Containers for hyperpolarized gases and associated methods

ABSTRACT

A resilient container configured to receive a quantity of hyperpolarized noble gas includes a wall with at least two layers, a first layer with a surface which minimizes spin-relaxation and a first or second layer which is substantially impermeable to oxygen. The container is especially suitable for collecting and transporting  3  He. The resilient container can be configured to directly deliver the hyperpolarized noble gas to a target interface by deflating or collapsing the inflated resilient container. Related collection and transporting methods include forming the wall of the container and collecting the hyperpolarized gas in a way which minimizes its exposure to de-polarizing impurities. Also, a container includes a quantity of polarized gas and extends the T 1  life by configuring the wall of the container with a controlled thickness of the surface coating and overlays the interior with an exterior which is substantially impermeable to oxygen. In addition, an O-ring and seal is configured to minimize the depolarizing effect of the collection device. Also disclosed is a method for determining the gas solubility in an unknown polymer or liquid using the measured relaxation time of a hyperpolarized gas.

This invention was made with Government support under AFOSR Grant No.F41624-97-C-9001 and NIH Grant No. 1 R43 HL59022-01. The United StatesGovernment has certain rights in this invention.

FIELD OF THE INVENTION

The present invention relates to processing, storage, transport anddelivery containers for hyperpolarized noble gases.

BACKGROUND OF THE INVENTION

Conventionally, Magnetic Resonance Imaging ("MRI") has been used toproduce images by exciting the nuclei of hydrogen molecules (present inwater protons) in the human body. However, it has recently beendiscovered that polarized noble gases can produce improved images ofcertain areas and regions of the body which have heretofore producedless than satisfactory images in this modality. Polarized Helium 3 ("³He") and Xenon-129 ("¹²⁹ Xe") have been found to be particularly suitedfor this purpose. Unfortunately, as will be discussed further below, thepolarized state of the gases are sensitive to handling and environmentalconditions and, undesirably, can decay from the polarized staterelatively quickly.

Hyperpolarizers are used to produce and accumulate polarized noblegases. Hyperpolarizers artificially enhance the polarization of certainnoble gas nuclei (such as ¹²⁹ Xe or ³ He) over the natural orequilibrium levels, i.e., the Boltzmann polarization. Such an increaseis desirable because it enhances and increases the MRI signal intensity,allowing physicians to obtain better images of the substance in thebody. See U.S. Pat. No. 5,545,396 to Albert et al., the disclosure ofwhich is hereby incorporated herein by reference as if recited in fullherein.

In order to produce the hyperpolarized gas, the noble gas is typicallyblended with optically pumped alkali metal vapors such as rubidium("Rb"). These optically pumped metal vapors collide with the nuclei ofthe noble gas and hyperpolarize the noble gas through a phenomenon knownas "spin-exchange". The "optical pumping" of the alkali metal vapor isproduced by irradiating the alkali-metal vapor with circularly polarizedlight at the wavelength of the first principal resonance for the alkalimetal (e.g., 795 nm for Rb). Generally stated, the ground state atomsbecome excited, then subsequently decay back to the ground state. Undera modest magnetic field (10 Gauss), the cycling of atoms between theground and excited states can yield nearly 100% polarization of theatoms in a few microseconds. This polarization is generally carried bythe lone valence electron characteristics of the alkali metal. In thepresence of non-zero nuclear spin noble gases, the alkali-metal vaporatoms can collide with the noble gas atoms in a manner in which thepolarization of the valence electrons is transferred to the noble-gasnuclei through a mutual spin flip "spin-exchange".

After the spin-exchange has been completed, the hyperpolarized gas isseparated from the alkali metal prior to introduction into a patient toform a non-toxic or sterile composition. Unfortunately, during and aftercollection, the hyperpolarized gas can deteriorate or decay (lose itshyperpolarized state) relatively quickly and therefore must be handled,collected, transported, and stored carefully. The "T₁ " decay constantassociated with the hyperpolarized gas' longitudinal relaxation time isoften used to describe the length of time it takes a gas sample todepolarize in a given container. The handling of the hyperpolarized gasis critical, because of the sensitivity of the hyperpolarized state toenvironmental and handling factors and the potential for undesirabledecay of the gas from its hyperpolarized state prior to the planned enduse, i.e., delivery to a patient. Processing, transporting, and storingthe hyperpolarized gases--as well as delivery of the gas to the patientor end user--can expose the hyperpolarized gases to various relaxationmechanisms such as magnetic gradients, ambient and contact impurities,and the like.

Typically, hyperpolarized gases such as ¹²⁹ Xe have been collected inrelatively pristine environments and transported in specialty glasscontainers such as rigid Pyrex™ containers. Flyperpolarized gas such as³ He has also been transported in Tedlar™ bags. Unfortunately, theseconventional transport containers have produced relatively shortrelaxation times or can require relatively complex gas extractionsystems which often leaves relatively large residual amounts of the gasin the container at the end use point.

One way of inhibiting the decay of the hyperpolarized state is presentedin U.S. Pat. No. 5,612,103 to Driehuys et al. entitled Coatings forProduction of Hyperpolarized Noble Gases. Generally stated, this patentdescribes the use of a modified polymer as a surface coating on physicalsystems (such as a Pyrex™ container) which contact the hyperpolarizedgas to inhibit the decaying effect of the surface of the collectionchamber or storage unit. However, there remains a need to address andrefine dominant and sub-dominant relaxation mechanisms and to decreasethe amount of physical systems required to deliver the hyperpolarizedgas to the desired subject. Minimizing the effect of one or more ofthese factors can increase the life of the product by increasing theduration of the hyperpolarized state. Such an increase is desired sothat the hyperpolarized product can retain sufficient polarization toallow effective imaging at delivery when transported over longertransport distances and for longer time periods from the initialpolarization than has been viable previously.

OBJECTS AND SUMMARY OF THE INVENTION

In view of the foregoing, it is an object of the present invention toprocess and collect hyperpolarized gas in improved containers which areconfigured to inhibit de-polarization in the collected polarized gas.

It is another object of the present invention to provide an improvedcontainer which can be configured to act as both a transport containerand a delivery mechanism to reduce the amount of handling or physicalinteraction required to deliver the hyperpolarized gas to a subject.

It is a further object of the present invention to provide an improved,relatively non-complex and economical container which can prolong thepolarization life of the gas in a container and reduce the amount ofpolarization lost during transport and delivery.

It is yet another object of the invention to provide methods, surfacematerials and containers which will minimize the de-polarizing effectsof the hyperpolarized state of the gas (especially ³ He) attributed toone or more of paramagnetic impurities, oxygen exposure, stray magneticfields, and surface relaxation.

It is an additional object of the present invention to provide a methodto determine the gas solubility in polymers or liquids with respect tohyperpolarized ¹²⁹ Xe or ³ He.

These and other objects are satisfied by the present invention which isdirected to a resilient container and/or gas contact surfaces which areconfigured to reduce surface or contact depolarization by forming aninner contact surface of a first material of a predetermined thicknesswhich acts to minimize the associated surface or contact depolarization.In particular, a first aspect of the invention is directed to acontainer for receiving a quantity of hyperpolarized gas. The containerincludes at least one wall comprising inner and outer layers configuredto define an enclosed chamber for holding a quantity of hyperpolarizedgas. The inner layer has a predetermined thickness and an associatedrelaxivity value which inhibits contact induced polarization loss of thehyperpolarized gas, and the outer layer defines an oxygen shieldoverlying the inner layer and is configured to minimize the migration ofoxygen into the container. Of course, the two layers can be integratedinto one if the material chosen acts both as a polarization friendlycontact surface and which is also resistant to the introduction ofoxygen molecules into the chamber of the container. The container alsoincludes a quantity of hyperpolarized noble gas and a port attached tothe wall in fluid communication with the chamber for capturing andreleasing the hyperpolarized gas therethrough. Preferably, the innerlayer thickness ("L_(th) ") is at least as thick as the polarizationdecay length scale ("L_(p) ") which can be determined by the equation:

    L.sub.p =√T.sub.p D.sub.p

where T_(p) is the noble gas nuclear spin relaxation time in the polymerand D_(p) is the noble gas diffusion coefficient in the polymer.

Advantageously, using a contact surface which has a thickness which islarger than the polarization decay length scale can minimize or evenprevent the hyperpolarized gas from sampling the substrate (the materialunderlying the first layer). Indeed, for hyperpolarized gases which canhave a high diffusion constant (such as ³ He), surfaces with polymercoatings substantially thinner than the polarization decay length scalecan have a more detrimental effect on the polarization than surfaceshaving no such coating at all. This is because the polarized gas can beretained within the underlying material and interact with the underlyingor substrate material for a longer time, potentially causing moredepolarization than if the thin coating is not present.

In a preferred embodiment, the container of the instant invention isconfigured to receive hyperpolarized ³ He and the inner layer is atleast 16-20 microns thick. In another preferred embodiment, thecontainer is an expandable polymer bag. Preferably, the polymer bagincludes a metallized coating positioned over the polymer whichsuppresses the migration of oxygen into the polymer and ultimately intothe polarized gas holding chamber. Advantageously, the capturedhyperpolarized gas can be delivered to the inhalation interface of asubject by exerting pressure on the bag to collapse the bag and causethe gases to exit the chamber. This, in turn, removes the requirementfor a supplemental delivery mechanism. It is additionally preferred thatthe container use seals such as O-rings which are substantially free ofparamagnetic impurities. The proximate position of the seal with thehyperpolarized gas can make this component a dominant factor in thedepolarization of the gas. Accordingly, it is preferred that the seal orO-ring be formed from substantially pure polyethylene or polyolefinssuch as ethylene, propylene, copolymers and blends thereof. Of course,fillers which are friendly to the hyperpolarization can be used (such assubstantially pure carbon black and the like). Alternatively, the O-ringor seal can be coated with a surface material such as LDPE or deuteratedHDPE or other low-relaxivity property material.

Similar to the preferred embodiment discussed above, another embodimentof the present invention is a resilient container for holdinghyperpolarized gas. The container comprises a first layer of a firstmaterial configured to define an expandable chamber to hold a quantityof hyperpolarized gas therein. Preferably, the first layer has apredetermined thickness sufficient to inhibit surface or contactdepolarization of the hyperpolarized gas held therein wherein the firstlayer material has a relaxivity value "Υ". Also preferably, therelaxivity value "Υ" is less than about 0.0012 cm/min for ³ He and lessthan about 0.01 cm/min for ²⁹ Xe. The container also includes a secondlayer of a second material positioned such that the first layer isbetween the second layer and the chamber, wherein the first and secondlayers are concurrently responsive to the application of pressure andone of the first and second layers acts as an oxygen shield to suppressoxygen permeability into the chamber. Additional layers of materials canbe positioned intermediate the first layer and the second layer. In onepreferred embodiment, hyperpolarized gas has a low relaxivity value inthe first layer material and the second layer preferably comprises amaterial which can shield the migration of the oxygen into the firstlayer. In another preferred embodiment, the resilient container has afirst layer formed of a metal film (which can act both as an oxygenshield and contact surface). In this embodiment, it is preferred thatthe relaxivity values are less than about 0.0023 and 0.0008 for ¹²⁹ Xeand ³ He respectively. Stated differently, it is preferred that thehypcrpolarized gas have a high mobility on the metal surface or smallabsorption energy relative to the metal contact surface such that the T₁of the gas in the container approaches >50% of its theoretical limit.

Another aspect of the invention is a method of inhibiting thedepolarization of a quantity of captured hyperpolarized gas. Theinternal surface of a chamber configured to receive a quantity ofhyperpolarized gas is coated or formed with a predetermined thickness ofa material having low relaxivity value for the hyperpolarized gas. Thecoating thickness is at least as thick as the polarization decay lengthscale ("L_(p) ") expressed by the equation stated above. Preferably, thecoating or material layer thickness is greater than a plurality of thepolarization decay length scale. Alternately, in another embodiment, theinternal surface of a resilient container is formed from a highpuritynon-magnetic metal film.

An additional aspect of the present invention is directed to a methodfor storing, transporting and delivering hyperpolarized gas to a target.The method includes introducing a quantity of hyperpolarized gas into acontainer. The container has a wall comprising a material resistant tothe transport of oxygen into the container. Preferably, the container isexpanded to capture the quantity of hyperpolarized gas. The container issealed to contain the hyperpolarized gas therein. The container istransported to a site remote from the hyperpolarization site. Thehyperpolarized gas is delivered to a target by compressing the chamberand thereby forcing the hyperpolarized gas to exit therefrom.Preferably, in order to maintain the hyperpolarized state, the containeris substantially continuously, from the time of polarization to thedelivery, either shielded or exposed to a proximately maintainedmagnetic field to protect it from undesired external magnetic fields.Further preferably, the container can be re-used (afterre-sterilization) to ship additional quantities of hyperpolarized gases.

Another aspect of the present invention is a method of inhibiting thedepolarization of hyperpolarized gas in a container configured tocollect a quantity of hyperpolarized gas. The method includes forming aseal from a material which is substantially free of paramagneticimpurities to inhibit the depolarization effect attributed to itsproximate location to the hyperpolarized gas in the container.

Similarly, a further aspect of the present invention is a valve forcontainers configured to releasably capture hyperpolarized gases. Thevalve comprises an entry port configured to engage with a hyperpolarizedgas chamber. The entry port has a passage in fluid communication withthe container. The valve also includes a valve member having open andclosed positions and a seal operably associated with the valve and thecontainer, wherein the seal is proximate to the hyperpolarized gas, andwherein the seal is formed from a material which is substantially freeof paramagnetic impurities or which is coated with a material which hasa low relaxivity value relative to the hyperpolarized gas.

An additional aspect of the present invention is a method for preparingan expandable storage container for receiving a quantity ofhyperpolarized gas. The method includes providing a quantity of purgegas into the hyperpolarized gas container and expanding thehyperpolarized gas container. The container is then collapsed to removethe purge gas. The oxygen in the container walls is outgassed bydecreasing the oxygen partial pressure in the container thereby causinga substantial amount of the oxygen trapped in the walls of the containerto migrate into the chamber of the container in the gas phase where itcan be removed. Preferably, after the outgassing step, the container isfilled with a quantity of storage gas such as nitrogen. The gas isintroduced into the container at a pressure which minimizes the pressuredifferential across the walls of the container to minimize furtheroutgassing of the container. Preferably, the container is then storedfor future use (temporally spaced apart from the time ofpreconditioning). The storage nitrogen and outgassed oxygen are removedfrom the container before filling with a quantity of hyperpolarized gas.Preferably, after removal from storage and prior to use, the nitrogen isremoved by evacuating the container before filling with a quantity ofhyperpolarized gas.

Yet another aspect of the present invention is directed to a method forshielding the hyperpolarized noble gas from stray magnetic fields.Preferably, the method includes shifting the normal frequency associatedwith the hyperpolarized gas to a frequency substantially outside thebandwidth of prevalent stray oscillating fields found in vehicles andother sources.

Another aspect of the present invention is directed to a method fordetermining the hyperpolarized gas (¹²⁹ Xe or ³ He) solubility in a(unknown) polymer or a particular fluid. The method includes introducinga first quantity of hyperpolarized noble gas into a container having aknown free volume and measuring a first relaxation time of thehyperpolarized gas in the container. A sample of desired material ispositioned into the container and a second quantity of hyperpolarizednoble gas is introduced into the container. A second relaxation time ofthe second hyperpolarized gas is measured in the container with thesample material. The gas solubility of the sample is determined based onthe difference between the two measured relaxation times. The materialsample can be a structurally rigid sample (geometrically fixed) with aknown geometric surface area/volume which is inserted into the freevolume of the chamber or container. Alternatively, the material samplecan be a liquid which partially fills chamber.

Advantageously, the methods and containers of the present invention canimprove the relaxation time (lengthen T₁) of the hyperpolarized gas bycontacting the hyperpolarized gas with a hyperpolarized contact surfacehaving a specified depth of a low-relaxivity value material relative tothe hyperpolarized noble gas. Further advantageously, the containeritself can be configured to provide the contact surface by forming thecontainer out of a resilient material such as a polymer bag. Thisconfiguration provides a relatively non-complex container which canconveniently be re-used. Alternatively, the internal surface of acontainer can be formed from a high purity metal providing the contactsurface. Additionally, the collapsible containers can be used to deliverthe gas into the patient interface without the need for additionaldelivery vehicles/equipment. This can reduce the exposure, handling, andphysical manipulation of the hyperpolarized gas which, in turn, canincrease the polarization life of the hyperpolarized gas. Resilientcontainers with high purity contact surfaces can be extremelyadvantageous for both ¹²⁹ Xe and ³ He as well as other hyperpolarizedgases; however, the expandable polymer container and coatings/layers areespecially suited for hyperpolarized ³ He. Further, the instantinvention can shield the hyperpolarized gas in a shipping container fromstray magnetic fields, especially deleterious oscillating fields whichcan easily dominate other relaxation mechanisms.

Additionally, the present invention can be used to determine the gassolubility in polymers or fluids which in the past has proven difficultand sometimes inaccurate, especially for helium.

Advantageously, the present invention now provides a way to model thepredictive behavior of surface materials and is particularly suited todetermining the relaxation properties of polymers used as contactmaterials in physical systems used to collect, process, or transporthyperpolarized gases. For example, the present invention successfullyprovides relaxation properties of various materials (measured and/orcalculated). These relaxation values can be used to determine therelaxation time (T₁) of hyperpolarized gas in containers correspondingto the solubility of the gas, the surface area of the contact material,and the free gas volume in the container. This information can beadvantageously used to extend the hyperpolarized life of the gas incontainers over those which were previously achievable in high-volumeproduction systems.

The foregoing and other objects and aspects of the present invention areexplained in detail herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a spin-down station used to measurerelaxation times according to one aspect of the present invention.

FIG. 2 is a graph showing the polarization level of a gas associatedwith the distance x the gas moves into a polymer.

FIG. 3 is a graph showing the results of the standardized relaxationtimes plotted against solubility (measured and theoretical) for variousmaterials (T₁ ^(cc) representing the relaxation time for ¹²⁹ Xehyperpolarized gas in a one cubic centimeter sphere).

FIG. 4 is a graph similar to FIG. 3 showing the results of standardizedrelaxation times for ³ He.

FIG. 5 is a detailed chart of predicted material values for Xenon andHelium.

FIG. 6 is a detailed chart of experimental material values for Xenon andHelium.

FIG. 7 is a perspective view of a hyperpolarized gas container accordingto one embodiment of the present invention in a deflated state.

FIG. 8 is a perspective view of the container of FIG. 7, shown in aninflated state.

FIG. 9 is a sectional view of the container shown in FIG. 7 according toone embodiment of the present invention.

FIG. 10 is an enlarged partial cutaway section view of the containerwall according to another embodiment of the present invention.

FIG. 11 is an enlarged partial cutaway section view of an additionalembodiment of a container wall according to the present invention.

FIG. 12 is an enlarged partial cutaway section view of yet anotherembodiment of a container wall according to the present invention.

FIG. 13 is a perspective view of a preferred embodiment of a containerwith a seal according to the present invention.

FIG. 14 illustrates the container of FIG. 13 with an alternativeexternal seal according to an additional embodiment of the presentinvention.

FIG. 15 illustrates another container with an alternative sealarrangement according to another embodiment of the present invention.

FIG. 15A is an exploded view of the container shown in FIG. 15.

FIG. 16 is a side perspective view of a shielded shipping receptacleconfigured to receive the container according to one embodiment of thepresent invention.

FIG. 17 is a schematic illustration of the resilient container of FIG.13 shown attached to a user interface adapted to receive the containerfor delivering the hyperpolarized gas therein to the user according toone embodiment of the present invention.

FIG. 18 shows the container of FIG. 17 in a deflated condition afterforces on the container cause the hyperpolarized gas to exit thecontainer and enter the target.

FIG. 19 is a schematic illustration of the container of FIG. 15 shownattached to a user interface according to one embodiment of the presentinvention.

FIG. 20 is a block diagram of a method for determining gas solubility ina polymer according to one embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will now be described more fully hereinafter withreference to the accompanying figures, in which preferred embodiments ofthe invention are shown. This invention may, however, be embodied inmany different forms and should not be construed as limited to theembodiments set forth herein. Like numbers refer to like elementsthroughout. Layers and regions may be exaggerated for clarity. For easeof discussion, the term "hyperpolarized gas" will be used to describe ahyperpolarized gas alone, or a hyperpolarized gas which contacts orcombines with one or more other components whether gaseous, liquid, orsolid. Thus, the hyperpolarized gas described herein can be ahyperpolarized gas composition/mixture (non-toxic such that it issuitable for in vivo introduction) such that the hyperpolarized noblegas can be combined with other noble gases and/or other inert or activecomponents. Also, as used herein, the term "hyperpolarized gas" caninclude a product where the hyperpolarized gas is dissolved into anotherliquid (such as a carrier) or processed such that it transforms into asubstantially liquid state, i.e., "a liquid polarized gas". Thus,although the term includes the word "gas", this word is used to name anddescriptively track the gas produced via a hyperpolarizer to obtain apolarized "gas" product. In summary, as used herein, the term "gas" hasbeen used in certain places to descriptively indicate a hyperpolarizednoble gas which can include one or more components and which may bepresent in one or more physical forms.

Preferred hyperpolarized noble gases (either alone or in combination)are listed in Table I. This list is intended to be illustrative andnon-limiting.

                  TABLE I                                                         ______________________________________                                        Hyperpolarizable Noble Gases                                                                 Natural                                                                       Abundance Nuclear                                              Isotope        (%)       Spin                                                 ______________________________________                                        .sup.3 He      ˜10.sup.-6                                                                        1/2                                                  .sup.21 Ne     0.27      3/2                                                  .sup.83 Kr     11.5      9/2                                                  .sup.129 Xe    26.4      1/2                                                  .sup.131 Xe    21.2      3/2                                                  ______________________________________                                    

Hyperpolarization

Various techniques have been employed to polarize, accumulate andcapture polarized gases. For example, U.S. Pat. No. 5,642,625 to Cateset al. describes a high volume hyperpolarizer for spin polarized noblegas and U.S. patent application Ser. No. 08/622,865 to Cates et al.describes a cryogenic accumulator for spin-polarized ¹²⁹ Xe. Thedisclosures of this patent and application are hereby incorporatedherein by reference as if recited in full herein. As used herein, theterms "hyperpolarize" and "polarize" are used interchangeably and meanto artificially enhance the polarization of certain noble gas nucleiover the natural or equilibrium levels. Such an increase is desirablebecause it allows stronger imaging signals corresponding to better MRIimages of the substance and a targeted area of the body. As is known bythose of skill in the art, hyperpolarization can be induced byspin-exchange with an optically pumped alkali-metal vapor oralternatively by metastability exchange. See U.S. Pat. No. 5,545,396 toAlbert et al. The alkali metals capable of acting as spin exchangepartners in optically pumped systems include any of the alkali metals.Preferred alkali metals for this hyperpolarization technique includeSodium-23, Potassium-39, Rubidium-85, Rubidium-87, and Cesium-133.Alkali metal isotopes, and their relative abundance and nuclear spinsare listed in Table II, below. This list is intended to be illustrativeand non-limiting.

                  TABLE II                                                        ______________________________________                                        Alkali Metals Capable of Spin Exchange                                                       Natural                                                                       Abundance Nuclear                                              Isotope        (%)       Spin                                                 ______________________________________                                        .sup.23 Na     100       3/2                                                  .sup.39 K      93.3      3/2                                                  .sup.85 Rb     72.2      5/2                                                  .sup.87 Rb     27.8      3/2                                                  .sup.133 Cs    100       7/2                                                  ______________________________________                                    

Alternatively, the noble gas may be hyperpolarized using metastabilityexchange. (See e.g., Schearer L D, Phys Rev, 180:83 (1969); Laloe F,Nacher P J, Leduc M, and Schearer L D, AIP ConfProx #131 (Workshop onPolarized ³ He Beams and Targets) (1984)). The technique ofmetastability exchange involves direct optical pumping of, for example,³ He without need for an alkali metal intermediary. The method ofmetastability exchange usually involves the excitation of ground state ³He atoms (1¹ S₀) to a metastable state (2³ S₁) by weak radio frequencydischarge. The 2³ S₁ atoms are then optically pumped using circularlypolarized light having a wavelength of 1.08 μm in the case of ³ He. Thelight drives transitions up to the 2³ P states, producing highpolarizations in the metastable state to which the 2³ S atoms thendecay. The polarization of the 2³ S₁ states is rapidly transferred tothe ground state through metastability exchange collisions betweenmetastable and ground state atoms. Metastability exchange opticalpumping will work in the same low magnetic fields in which spin exchangepumping works. Similar polarizations are achievable, but generally atlower pressures, e.g., about 0-10 Torr.

Generally described, for spin-exchange optically pumped systems, a gasmixture is introduced into the hyperpolarizer apparatus upstream of thepolarization chamber. Most xenon gas mixtures include a buffer gas aswell as a lean amount of the gas targeted for hyperpolarization and ispreferably produced in a continuous flow system. For example, forproducing hyperpolarized ¹²⁹ Xe, the pre-mixed gas mixture is about95-98% He, about 5% or less ¹²⁹ Xe, and about 1% N₂. In contrast, forproducing hyperpolarized ³ He, a mixture of 99.25% ³ He and 0.75% N₂ ispressurized to 8 atm or more and heated and exposed to the optical laserlight source in a batch mode system. In any event, once thehyperpolarized gas exits the pumping chamber it is directed to acollection or accumulation container.

A 5-20 Gauss alignment field is typically provided for the opticalpumping of Rb for both ¹²⁹ Xe and ³ He polarization. The hyperpolarizedgas is collected (as well as stored, transported, and preferablydelivered) in the presence of a magnetic field. It is preferred forsolid (frozen) ¹²⁹ Xe that the field be on the order of at least 500Gauss, and typically about 2 kilo Gauss, although higher fields can beused. Lower fields can potentially undesirably increase the relaxationrate or decrease the relaxation time of the polarized gas. As regards ³He, the magnetic field is preferably on the order of at least 5-30 gaussalthough, again, higher (homogeneous) fields can be used. The magneticfield can be provided by electrical or permanent magnets. In oneembodiment, the magnetic field is provided by a plurality of permanentmagnets positioned about a magnetic yoke which is positioned adjacentthe collected hyperpolarized gas. Preferably, the magnetic field ishomogeneously maintained around the hyperpolarized gas to minimize fieldinduced degradation.

Polarized Gas Relaxation Processes

Once hyperpolarized, there is a theoretical upper limit on therelaxation time (T₁) of the polarized gas based on the collisionalrelaxation explained by fundamental physics, i.e., the time it takes fora give sample to decay or depolarize due to collisions of thehyperpolarized gas atoms with each other absent other depolarizingfactors. For example, ³ He atoms relax through a dipole-dipoleinteraction during ³ He--³ He collisions, while ¹²⁹ Xe atoms relaxthrough N·I spin rotation interaction (where N is the molecular angularmomentum and I designates nuclear spin rotation) during ¹²⁹ Xe--¹²⁹ Xecollisions. Stated differently, the angular momentum charge associatedwith flipping a nuclear spin over is conserved by being taken up by therotational angular momentum of the colliding atoms. In any event,because both processes occur during noble gas-noble gas collisions, bothresulting relaxation rates are directly proportional to gas pressure (T₁is inversely proportional to pressure). Thus, at one atmosphere, thetheoretical relaxation time (T₁) of ³ He is about 744-760 hours, whilefor ¹²⁹ Xe the corresponding relaxation time is about 56 hours. SeeNewbury et al., Gaseous ³ He--³ He Magnetic Dipolar Spin Relaxation, 48Phys. Rev. A., No. 6, p. 4411 (1993); Hunt et al., Nuclear MagneticResonance of ¹²⁹ Xe in Natural Xenon, 130 Phys Rev. p. 2302 (1963).Unfortunately, other relaxation processes prevent the realization ofthese theoretical relaxation times. For example, the collisions ofgaseous ¹²⁹ Xe and ³ He with container walls ("surface relaxation") havehistorically dominated most relaxation processes. For ³ He, most of theknown longer relaxation times have been achieved in special glasscontainers having a low permeability to helium. In the past, afundamental understanding of surface relaxation mechanisms has beenelusive which has made the predictability of the associated T₁difficult.

U.S. Pat. No. 5,612,103 to Driehuys et al. describes using coatings toinhibit the surface-induced nuclear spin relaxation of hyperpolarizednoble gases, especially ¹²⁹ Xe. The contents of this patent are herebyincorporated by reference as if recited in full herein. Driehuys et al.recognized that nuclear spin relaxation of ¹²⁹ Xe on apolydimethoylsiloxane ("PDMS") surface coating can be dominated bydipolar coupling of the ¹²⁹ Xe nuclear spin to the protons in thepolymer matrix. Thus, it was demonstrated that paramagnetic contaminants(such as the presence of paramagnetic molecules like oxygen) were notthe dominant relaxation mechanism in that system because theinter-nuclear dipole-dipole relaxation was found to dominate the systemunder investigation. This was because ¹²⁹ Xe substantially dissolvedinto the particular polymer matrix (PDMS) under investigation. SeeBastiaan Driehuys et al., Surface Relaxation Mechanisms ofLaser-Polarized ¹²⁹ Xe, 74 Phys. Rev. Lett., No. 24, pp. 943-4946(1995).

One aspect of the instant invention now provides a more detailedunderstanding of noble gas depolarization on polymer surfaces. Indeed,as will be explained further below, noble gas solubility in largenumbers of polymer systems (not just PDMS) can cause inter-nucleardipole-dipole relaxation to dominate the polarization decay rate.Notably, this insight now indicates that polymers can be especiallyeffective for the suppression of ³ He relaxation. In addition, apredictive explanation of noble gas relaxation on polymer surfaces isdiscussed below. Advantageously, it is now possible to calculate andmeasure the relaxation properties of various materials. This informationcan be advantageously used with other parameters such as free gas volumeand surface area of containers to provide more effective andadvantageous surface configurations and material characteristics whichcan facilitate, preserve, and further improve the polarization life ofthe noble gas. This is especially useful in providing containers whichcan yield reliable, repeatable, and predictable high-volume polarizationproduction performance which in the past has been difficult to achieveoutside the pristine conditions of a small production laboratory.

Generally stated, magnetic interactions can alter the time constant ofrelaxation, referred to as the longitudinal relaxation time (T₁), andtypically occur when different atoms encounter one another. In the caseof hyperpolarized noble gases held in containers, the nuclear magneticmoments of the gas atoms interact with the surface materials to returnthe gas to the equilibrium or non-hyperpolarized state. The strength ofthe magnetic moment can be a determinative factor in determining therelaxation rate associated with the surface material. Since differentatoms and molecules have different magnetic moments, relaxation ratesare material specific.

Relaxivity of Materials

In order to compare the characteristic information of certain materialsconcerning their respective relaxing effects on hyperpolarized noblegases, the term "relaxivity" is used. As used herein, the term"relaxivity" ("Υ") is used to describe a material property associatedwith the rate of depolarization ("1/T₁ ") of the hyperpolarized gassample. For a container having a chamber volume "Vc" capable of holdinga quantity of hyperpolarized gas and for a material sample with asurface area "A" in the container chamber, each time a polarized gasatom contacts the container surface, it has a probability ("p") ofdepolarizing. The rate of depolarization (1/T₁)of this gas sample in thechamber can then be described by p times the rate at which gas atomscollide with the surface ("R"). ##EQU1##

The average surface collision rate (R) per gas atom is known fromstatistical mechanics, R. Reif, Fundamentals of statistical and ThermalPhysics, McGraw-Hill (1965): ##EQU2## In this equation, "ν" is the meanthermal velocity of the gas atoms. For the case of a one cubiccentimeter ("1 cc") sphere of ¹²⁹ Xe the area is A=4πr² and the volumeis V=4πr3/3. Thus, for v=154 m/s, equation (2.2) yields a collision rateR=800 s⁻¹. In other words, each atom of Xe is contacting the surface ofthe sphere 800 times in 1 second. Therefore, according to equation (2.1)long T₁ times must have a minute probability for depolarization duringeach collision (p<<1). Substituting equation (2.2) back into equation(2.1) yields: ##EQU3##

Since measurements for this study are performed at room temperature, "ν"will not vary. Therefore, the relaxivity term, ("Υ") which is defined asΥ=vp/4, results in: ##EQU4##

Thus, relaxivity ("Υ") is a material property that can describe thedepolarizing effect that a specific material has on a hyperpolarized gassample.

When considering hyperpolarized gas containers, it is important tonotice the relationship between the 1/T₁ and A/V terms in Equation 2.4.Thus, the ratio "A/V" for a sphere with a radius "r", the ratio reducesto 3/r. Therefore, a one liter sphere (1000 cc, r=6.2 cm) has a T₁ thatis 10 times longer than a sphere with a one cubic centimeter volume (1cc, r=0.62 cm) made of the same material. Therefore, preferably, inorder to improve the T₁ of hyperpolarized gas in the containers, thecontainers are configured and sized to decrease the value of the ratioA/V--i.e., to increase the volume relative to the area of the container,as will be discussed further below.

Determining Relaxivity

Equation 2.4 can be used to calculate relaxivity of the gas if surfacerelaxation is the only (dominant) depolarizing effect at work. In thecase of practical material studies, this is not the case. The surfacesof the test chamber, the chamber seal, and other impurities alsocontribute to the relaxation of the gas. However, by using therelaxation time differences between hyperpolarized gas in an empty testchamber and the hyperpolarized gas in the chamber containing a materialsample positioned to contact the hyperpolarized gas, the characteristicrelaxivity of the material can be determined.

Note that the relaxation rates are additive in the following form:##EQU5##

In general form, T₁ ^(a) can represent the relaxation effect of the testchamber surface, T_(b) ¹ can represent the effect of the hyperpolarizedgas atoms colliding with one another, and so on. Assuming that surfacerelaxation is the dominant relaxation effect, the relaxation rate can bedescribed by adding the surface effects of the material sample and thetest chamber. ##EQU6## where A_(m) and Υ_(m) describes the area andrelaxivity respectively of the material sample and A_(c) and Υ_(c)correspond to the area and relaxivity of the container or chamber. "V"is the free gas volume in the chamber. In this case, V=V_(c) -V_(m),where "V_(c) " is the volume of the chamber and "V_(m) " is the volumeof the container occupied by the material sample. In relaxivity studiesfor new materials (where the material sample is small) the free volume"V" can be reasonably approximated as equal to V_(c), i.e. V=V_(c).Substituting back into (2.6): ##EQU7##

Note that for a chamber without a material sample, this equation reducesto: ##EQU8## where T_(1c) is the characteristic relaxation rate of thecontainer or empty chamber. Substituting (2.8) into (2.7) yields:##EQU9##

Solving equation (2.9) gives an expression for the relaxivity Υ_(m)associated with a specific material sample with a measured T₁ in achamber with known volume and observed T_(1c) : ##EQU10##

The relaxivity of a given material can easily be translated back into amore intuitive characteristic relaxation time. One method of comparison,in keeping with past surface relaxation rate studies, is to describe therelaxation rate as if there were a 1 cc spherical cell made of thematerial in question. Knowing the volume and surface area of such a cell(A=4πr², V=4πr³ /3, r=0.62 cm) and substituting back into (2.8):##EQU11## Again, this container geometry is for illustration as itstandardizes the relaxation term for comparison with past data. Forreference, observed T₁ values from ¹²⁹ Xe studies in the past showedultra clean Pyrex with a Rb monolayer surface to have an associatedT^(cc) ₁ =30 minutes.

Experimental Determination of Relaxivity

The hyperpolarized gas samples were used in a materials testing centerknown as the Spin Down Station. This apparatus was constructed to testvarious material samples in a controlled environment. The systemconsists of a materials testing chamber, a Pulse-NMR Spectrometer, and aLab View user interface. The flexible system allows various chambers orbags to be cleaned and filled with polarized ¹²⁹ Xe or ³ He. ThePulse-NMR system then charts the relaxation of signal from thesecontainers over time.

Equipment Layout

FIG. 1 is a schematic diagram of the Spin Down Station. This apparatusconsists of a Helmholtz pair generating a stable Helmholtz magneticfield 151 around the glass test chamber labeled the Spin Down Chamber152. The signal response frequency (f) is proportional to the appliedmagnetic field (B₀) expressed by the equation (f=γB₀ /2π). Thisproportionally constant is known as the gyromagnetic ratio (γ_(He) =7400s⁻¹ G⁻¹, γ_(Xe) =26700 s⁻¹ G⁻¹). If the applied magnetic field remainsconstant, the coil must be tuned to switch between the two gases. As analternative to retuning, the field strength was adjusted to result inthe same frequency response for both gases. A current of 1.0 A (7 Gfield) for ³ He and 2.5 A (21 G field ) for ¹²⁹ Xe was applied to theHelmholtz pair noted by the Helmholtz field shown in FIG. 1. In thecenter of Helmholtz field 151 rested one of the two spin down chambers152 used in these tests. Both chambers were valved to evacuate (basepressure ˜30 miliTorr) and fill the chamber with hyperpolarized gas.Each chamber could be opened to insert polymer samples (typically 10mm×20 mm×1 mm). As shown, the NMR coil 153 rests beneath the chamber inthe center of the Helmholtz field 151.

The first spin down chamber was made of Pyrex™ coated with dimethyldichlorosilane (DMDCS) and used a Teflon™ coated rubber O-ring as thevacuum seal. This chamber had a 110 minute characteristic T_(1c)suitable for observing the surface relaxation effects of various polymersamples 154. Notably, after numerous tests, the T_(1c) would oftendecrease. A thorough cleaning with high-purity ethanol restored thechamber to the baseline value. Unfortunately, the T_(1c) for the Pyrex™chamber with ³ He was not long enough to distinguish good from badmaterials for ³ He. Tests of various glasses in the Pyrex™ spin downchamber showed that a chamber made of 1724 aluminosilicate glass wouldhave a sufficiently long T_(1c) for ³ He.

The 1724 ³ He chamber was constructed with a ground seal requiringApiezon™ vacuum grease. The chamber had a characteristic T_(1c) of 12hour on average. The Apiezon™ grease used to seal both the chamber andthe entry valve caused the chamber T_(1c) to fluctuate significantlymore than the Pyrex™ chamber. To restore the chamber to baseline T_(1c)the grease was removed by cleaning the chamber with high-purity Hexane.

Testing Procedure

Using the Spin Down Station, seven polymer samples were tested usinghyperpolarized ¹²⁹ Xe or ³ He. These polymers were purchased fromGoodfellow, Inc., Berwyn, Pa.

    ______________________________________                                                                          Thickness                                                            Thickness                                                                              (mm)                                                                 (mm)     (Sorption                                   Material      Density    (T.sub.1 study)                                                                        study)                                      ______________________________________                                        Polyamide     1.13       1        0.012*                                      (Nylon 6)                                                                     Silicone Elastomer                                                                          1.1-1.3    1        1                                           High Density Polyethylene                                                                   0.95       1        0.01                                        (HDPE)                                                                        Low Density Polyethylene                                                                    0.92       1        0.05                                        (LDPE)                                                                        Polyimide     1.42       1        0.025                                       (Kapton)                                                                      Polypropylene 0.9        1        0.01                                        (PP)                                                                          Polytetrafluoroethylene                                                                     2.2        1        0.01                                        (PTFE)                                                                        ______________________________________                                         *Sample provided by DuPont.                                              

The particular polymers were chosen to represent a wide range ofsolubilities to ¹²⁹ Xe and ³ He gases. Each polymer sample was cleanedwith ethanol and cut to a specific size and shape to provide a knownvolume and surface area of the polymer sample (normally V=2 cm³, SA=42.6cm²) for each T₁ study.

The following steps were taken for each material measurement:

1. Clean the testing chamber

2. Polarize ¹²⁹ Xe or ³ He

3. Perform a T₁ study to establish the chamber baseline (T_(1c))

4. Place polymer sample in chamber

5. Polarize ¹²⁹ Xe or ³ He

6. Perform a T₁ study of the chamber containing polymer same (T_(1s))

7. Use T_(1c) and T_(1s) to find relaxation rate due to specific polymer

The Polymer Sorption Model

The ability to measure and calculate relaxivity can result in anunderstanding of the physical characteristics that differentiatematerials. An initial study of a wide range of materials confirmedconventional rigid containers of glass are much better than containersof materials containing paramagnetic or ferrous constituents such asstainless steel. Notably, this test also showed a wide range ofrelaxivities within different material groups. In particular, differentpolymer materials were observed across the relaxivity spectrum.Manufacturing concerns such as durability and reliability make polymermaterials an excellent alternative to the glass storage containers thatare typically used for hyperpolarized gases. Scientifically,substantially pure samples of these materials allow for relatively lesscomplex models of surface relaxation.

For discussion purposes, assume there is a polymer container ofhyperpolarized gas in a homogeneous magnetic field. Since polymers arepermeable materials, some quantity of gas dissolves in the containerwalls. The only dominant relaxation mechanism in this system is that ofthe hyperpolarized gas atoms interacting with the protons orcontaminants in the surface and bulk of the polymer container. Driehuyset al. demonstrated that relaxation of hyperpolarized ¹²⁹ Xe in aspecially coated glass sphere was dominated by the dipolar couplingbetween the protons in the surface and the ¹²⁹ Xe nuclear spin. SeeDriehuys et al., High-volume production of laser-polarized ¹²⁹ Xe, 69App. Phys. Lett. (12), p. 1668 (1996). Since Xe--Xe collisions have a 56hour T₁ and typical conventional material T₁ times are 2 hours or less,the relaxation rate of the free gas can be neglected. Gas dissolved inthe polymer surface relaxes quickly (<1 second), so most of thehyperpolarized gas in the container is in the free gas form. Therefore,relaxation of this gas occurs through continual exchange between thefree gas and the gas dissolved in the polymer. In material quantities,the rate of this gas exchange can be described by the "sorptionparameters"--solubility ("S"), diffusion coefficient ("D"), andpermeability ("P"). Permeability is the transmission of atoms ormolecules through a polymer film. It depends on chemical and physicalstructure of the material as well the structure and physicalcharacteristics of the permeant molecules. Permeability can be definedas the product of solubility and the diffusion coefficient. ("P=S×D").Solubility ("S") is a measure of how much permeant can be dissolved in agiven material. Diffusion coefficient ("D") is a measure of the randommobility of the atoms in the polymer. The polymer sorption parameterscan be used to characterize the relaxation of hyperpolarized gases inthe presence of permeable surfaces.

Relaxation in the Presence of Polymer Surfaces

Magnetization ("M") is defined as the product of the gas polarization"P" and the gas number density"[G]", M=[G]P. The equation governingrelaxation of magnetization in the presence of a surface diffusion##EQU12## where ("M(x,t)") is magnetization, ("D") is the diffusioncoefficient of the gas in the surface material, and ("Γ") is therelaxation rate of the gas. See W. Happer et al., Hyp. Int. 38, pp.435-470 (1987). As is customary, the solution is written as a product ofspatial and time dependent components: ##EQU13## where ("m(x)") is thespatial distribution of magnetization on the surface. Substituting(2.15) into (2.13) yields the spatial equation: ##EQU14##

This differential equation describes the spatial distribution ofmagnetization in the presence of diffusion and relaxation. Considering aone dimensional chamber shown in FIG. 2.

The chamber is a gas volume of width "2a" bounded on each side byinfinite polymer walls. The polarization of gas in this chamber has twospecific regions of interest. In the free gas portion of the container,the polarization is relatively homogenous with respect to spatialvariable x. In contrast, polarization drops exponentially with distancex into the polymer surface. This profile reflects a much fasterrelaxation rate inside the polymer as opposed to in free space.

Equation (2.14) can be used to solve for the spatial magnetization ofthe gas and polymer regions independently. For a gas phase withdiffusion coefficient D_(g) and intrinsic relaxation rate Γ_(g) =0.Equation (2.14) becomes: ##EQU15##

The first order symmetric solution to this equation is: ##EQU16##Similarly, the polymer region has diffusion coefficient "D_(p) " andrelaxation rate Γ_(p) : ##EQU17##

One simplifying assumption is that the relaxation rate in the polymer ismuch faster than the observed relaxation rate (Γ_(p) >>1/T₁). Thusneglecting 1/T₁ term in (2.16) yields a solution of the form: ##EQU18##

These two solutions in conjunction with the appropriate boundaryconditions can be used to solve for the observed T₁ of the gas in thepolymer chamber. The first boundary condition ("BC") maintainscontinuity of polarization across the polymer gas boundary. Recallingthat magnetization is the product of polarization and gas number densityyields: ##EQU19## where ("S") is defined as the ratio of gas numberdensities, or the Ostwald Solubility "S=N_(p) /N_(g) ". The secondaryboundary condition ("BC2") arises because the exchange of magnetizationacross the gas-polymer boundary is equal on both sides. This exchange,known as the magnetization current, is defined as J_(m) =-D∇m(x),yielding the boundary condition: ##EQU20##

Applying the boundary conditions to the solutions for magnetization ineach of the two regions yields the following transcendental equation:##EQU21##

This equation can be solved numerically, although a reasonableapproximation is that k_(g) a<<1, so that tan k_(g) a≈k_(g) a. Inphysical terms, this implies that the magnetization is spatially uniformacross the gas phase. It also considers only the slowest of multiplediffusion modes. In order for this assumption to be false, therelaxation rate at the walls would have to be fast compared to the timeit takes for the gas to diffuse across the chamber. Diffusion times aretypically a few seconds, while common T₁ values are several minutes.Applying this assumption yields: ##EQU22##

Substituting in k_(g) and k_(p) from the solutions to (2.15) and (2.16)gives: ##EQU23##

The relaxation rate in the polymer terms can be rewritten in terms ofΓ_(p) =1/T_(1p). Solving for the relaxation time T₁ : ##EQU24##

This analysis can be extended into three dimensions, yielding: ##EQU25##where V_(c) is the internal volume of the chamber, A is the exposedsurface area of the polymer and S is the solubility of the gas in thepolymer.

The inverse relationship between T₁ and S is a key observation from thisdevelopment. Because He solubilities are typically many orders ofmagnitude lower than corresponding Xe solubilities, T₁ times for ³ Heshould be significantly longer than for ¹²⁹ Xe. There is also anapparent inverse square root dependence on the diffusion coefficientD_(p). However, the relaxation time in the polymer 1/T_(p) also dependson D_(p), canceling the overall effect on T₁. This leaves solubility asthe dominant sorption characteristic in determining T₁.

Despite canceling out of (2.21) the diffusion coefficient plays asignificant role in another quantity of interest, the length scale ofthe gas and polymer interaction. The exponential decay length scale ofthe polarization L_(p) =1/k_(p) is given by the solution to (2.16):

    L.sub.p =√D.sub.p T.sub.1.sup.p                     (2.22)

Importantly, this scale describes the depth into the polymer that thegas travels in the relaxation time period. In order to comparetheoretical predictions to experimental data, it is preferred thatmaterial samples be at least several length scales thick. This ensuresthat the surface model developed here which assumes infinite polymerthickness is an accurate approximation of the diffusion process. Forreference, LDPE has a diffusion constant of 6.90e-6 cm² /s for He gasand hyperpolarized ³ He has a relaxation time in the polymer of about0.601 s (T₁ ^(p) =0.601 seconds). The resulting length scale is about 20μm, many times smaller than the 1 mm polymer samples used in the studydescribed herein.

Predicting T₁ Values Using Sorption Model

Using equation (2.21) to predict T₁ values for hyperpolarized gases inthe presence of various polymer surfaces requires knowledge of the testenvironment (V_(c),A_(p)), as well as parameters linking the specificgas and polymer (T₁ ^(p), S and D). Unfortunately, the solubility anddiffusion data linking gas and polymers is scattered and sometimesnonexistent. On the other hand, the test environment is typically known.Advantageously, this data can be used to calculate the T₁ ^(p).

As discussed earlier, the relaxation mechanism that dominateshyperpolarized gas relaxation in polymers is the interaction with thenuclear magnetic moments of the hydrogen nuclei (in hydrogen basedpolymers). Generally stated, in the absence of paramagneticcontaminants, the ¹ H nuclei are the only source of magnetic dipoles tocause relaxation. Based on this interaction, Huang and Freed developedan expression for the relaxation rate of spin 1/2 gas diffusing througha polymer matrix. See L. P. Hwang et al., Dynamic effects of paircorrelation functions on spin relaxation by translational diffusion inliquids, 63 J. Chem. Phys. No. 9, pp. 4017-4025 (1975); J. H. Freed,Dynamic effects ofpair correlation functions on spin relaxation bytranslational diffusion in liquids. II. Finite jumps and independent T₁processes, 68 J. Chem. Phys. Vol. 9, pp. 4034-4037 (1978); and E. J.Cain et al., Nuclear Spin Relation Mechanisms and Mobility of Gases inPolymers, 94 J. Phys. Chem. No. 5, pp. 2128-2135 (1990). This results inthe following expression in a low magnetic field B regime (B<1000Gauss). ##EQU26##

In this formula, γ_(g) is the gyromagnetic ratio of the noble gas, γ_(H)is the gyromagnetic ratio of the protons, s is the proton spin number(1/2). N_(a) is Avogadro's number, [¹ H] is the molar density of protonsin the matrix, and b is the distance of closest approach of the noblegas to a proton. The dipole interaction equations have an inverse squaredependence on the gyromagnetic ratios γ_(g) and γ_(h). As noted before,substituting this form into Equation (2.21) cancels D_(p) from therelaxation expression. This leaves only solubility (S) to effect the T₁in various polymers. The other significant factor in (2.23) is the [¹H]⁻¹ dependence. As such, since protons in the polymer are the dominantrelaxation mechanism, high concentrations will adversely affect T₁ ^(p).

Implementing this expression for T₁ ^(p) requires the appropriatephysical parameters in CGS units. Table 2.1 shows an example of theapproximate values used for this calculation performed for relaxation of¹²⁹ Xe in low-density polyethylene (LDPE):

                  TABLE 2.1                                                       ______________________________________                                        Sample Data for T.sub.1.sup.p of .sup.129.sub.Xe in LDPE                      ______________________________________                                                 γ.sub.g (G.sup.-1 s.sup.-1) =                                                    7.40e03                                                              γ.sub.h (G.sup.-1 s.sup.-1) =                                                    2.68e04                                                              h (erg s) =                                                                            6.63e-27                                                             [.sup.1 H] (mol/L) =                                                                   131.43                                                               b (cm) = 2.40e-08                                                             D.sub.g (cm.sup.2 s.sup.-1) =                                                          6.90e-08                                                             T.sub.1.sup.p (s) =                                                                    0.0653                                                      ______________________________________                                         *One of few available literature values (Polymer Handbook)               

Confirmation of Predictive Model

The development of the sorption based relaxation model along with theexperimental apparatus to test relaxivity allows the comparison of atheoretical model of surface relaxation with experimental results.Confirmation of this model enables quantitative predictions of surfacerelaxation for selecting appropriate and preferred materials to contacthyperpolarized gases. The spin down station was used to measure therelaxation effects of 7 different polymers on hyperpolarized ¹²⁹ Xe and³ He. In order to compare this experimental data with the theoretical,solubility of both gases in each polymer was measured. These sorptionmeasurements are described below as well as a discussion of results fromthe ¹²⁹ Xe and ³ He polymer studies.

Solubility Measurements

Solubility ("S") is the only remaining unknown in the formula to predictT₁ of hyperpolarized gases in polymers (2.21) the equation is relatedhere for reference: ##EQU27##

Sorption data for various polymers is tabulated in sources such as thePolymer Handbook. S. Pauly, Permeability and Diffusion Data, The PolymerHandbook VI/435. Unfortunately, while data for He is widely available(although prone to error), there has not been a need to measure sorptioncharacteristics of Xe in different polymers. The lack of published Xesolubilities resulted in a search for equipment to measure thesequantities. The polymer group at the Chemical Engineering Department atNorth Carolina State University measured the solubility of both Xe andHe gases in the 7 polymers that were to be used to verify the polymerrelaxation theory. The results of He and Xe solubility measurements arecompared to the available literature values in Table 4.1 below.

                  TABLE 4.1                                                       ______________________________________                                        Results of Solubility Measurements                                            S (Xe)         S (Xe)     S (He)    S (He)                                    (lit.)         (meas.)    (lit.)    (meas.)                                   ______________________________________                                        LDPE    0.59       0.68±   0.0055  0.006±                               HDPE    --         0.42±   0.0028  0.004±                               PP      --         0.70±   0.0002  0.020±                               PTFE    0.75       0.70±   0.1104  0.003±                               Nylon 6 --          .31       0.0043*  .003                                   Silicone                                                                              3.99       1.93±   0.0430  0.034±                               PI      --         4.00 ± 0.1                                                                            0.0056  0.030±                               ______________________________________                                         *Literature value for Nylon 11.                                          

The measurements were obtained by placing polymer samples in anevacuated chamber. A known pressure of gas was then introduced into thechamber. As the gas dissolved into the polymer, the decrease in chamberpressure was recorded. By knowing the volume of the test chamber andcarefully maintaining the temperature of the apparatus, the solubilityof the gas in the polymer can be calculated from the pressure vs. timedata. However, there are many intrinsic difficulties in polymer sorptionmeasurements. Because of the low diffusion coefficients in some polymerssuch as polyimide, it can take a long time for gas to permeate theentire sample and establish equilibrium. Even the thinnest samplesavailable must be allowed to remain in the chamber for many days.Another problem, evident in He measurements, is that pressuredifferences observed for materials with low solubilities are extremelysmall, resulting in significant measurement uncertainty. In additionthese to problems, density values play an important role in thesolubility calculation. While the manufacturer provides densityestimates for the material samples, laboratory measurements confirmedthat these values were often inaccurate. This discrepancy can beresponsible for dramatic changes in the final solubility value. Itshould therefore be noted that relative to the sorption measurements,more reliable results could be obtained. However, the values providedare sufficient to confirm the solubility based relaxation theory.

¹²⁹ Xe Materials Study

The majority of this materials study was performed using hyperpolarized¹²⁹ Xe. A much greater sensitivity of ¹²⁹ Xe to surface effects resultedin shorter T₁ times and allowed for more rapid testing of materials.More dramatic relaxation effects eliminate the need for an extremelylong chamber T₁ as is the case for ³ He studies. This fact aloneresulted in more reliable results for ¹²⁹ Xe materials testing.

FIG. 3 is a plot of T₁ ^(cc) vs. the product S[1H].sup..5, representingthe two significant terms in the expression for T₁ (2.21) developed inthe polymer sorption relaxation model. For the experimental data points,the y error bars on the graph represent the cumulative error in therelaxation measurement. The x error bars are associated with thesolubility measurements described above. The data confirms thatsolubility can be used to predict T₁ for hyperpolarized ¹²⁹ Xe onpolymer surfaces. While the experimental data points follow the trendpredicted by the theoretical model remarkably well, certaindiscrepancies merit further discussion.

Lower than predicted T₁ measurements as in the case of silicone can beexplained in several ways. Paramagnetic impurities in the materialsample or test chamber are the primary suspect. Recall that only protonswere assumed to have a depolarizing effect on the hyperpolarized gas. Inorder for this assumption to hold true, the composition of the materialsample would have to be extremely pure. For example, given that thegyromagnetic ratios of Fe and protons are related Υ_(Fe) ˜1000Υ_(1H), aone part per thousand presence of Fe in the material sample can doublethe relaxation rate. Although the sample surfaces were cleaned withhigh-purity ethanol prior to testing in the Spin Down Station,paramagnetic impurities can be trapped in the polymer matrix during thecuring process. One possible contaminant is Pt metal (which isparamagnetic) that can be used in the mold forming silicone polymers.

When considering factors that cause the measured T₁ results to be higherthan predicted as in the case of polyimide (PI) and PTFE, the diffusioncoefficient becomes an important parameter. For polyimide, the diffusionof Xe into the polymer is so slow that it takes weeks for the Xe toequilibrate completely. This time scale is much longer than the 1-2 hourtime scale of the relaxation measurements. Since the T₁ ^(p) of ¹²⁹ Xein PI is on the order of 100 ms (based on LDPE), the ¹²⁹ Xe atoms onlysample a tiny layer (˜5 μm, based on a diffusion coefficient D˜10⁻⁸ cm²/s), of the surface of the polymer sample. This surface layer may havedifferent sorption characteristics than the bulk polymer that was usedin the solubility measurements. While solubility can typically only bemeasured for the bulk sample, the region of interest is only 0.5 μm outof 1 mm, or 1/1000 of the actual sample.

A summary comparison of the predicted and measured results for ¹²⁹ Xe ispresented in Table 4.2. More detailed results from the theoretical andexperimental calculations are tabulated in FIG. 5.

                  TABLE 4.2                                                       ______________________________________                                        Results of Polymer Relaxation Study for .sup.129 Xe                                    Pred.                                                                         Υ (cm/                                                                        Pred. T.sub.1.sup.cc                                                                   Measured Υ                                                                      Measured T.sub.1.sup.cc                   S        min)    (min)    (cm/min)  (min)                                     ______________________________________                                        LDPE  0.68   0.0419  4.94   0.0370 ± 0.0039                                                                      5.59 ± 0.59                          HDPE  0.42   0.0263  7.87   0.0362 ± 0.0025                                                                      5.71 ± 0.39                          PP    0.70   0.0427  4.85   0.0540 ± 0.0035                                                                      3.83 ± 0.25                          PTFE  0.75   0.0356  5.82   0.0249 ± 0.0016                                                                      8.30 ± 0.54                          Nylon 6                                                                              .31    .0166  12.5   0.0104 ± 0.0016                                                                      19.91 ± 2.99                         Silicone                                                                            1.93   0.1066  1.94   0.3112 ± 0.0072                                                                      0.67 ± 0.02                          PI    4.10   0.1345  1.54   0.0212 ± 0.0017                                                                      9.78 ± 0.78                          ______________________________________                                    

³ He Material Studies

The study of ³ He surface relaxation on polymers is much morechallenging than the study of ¹²⁹ Xe. FIG. 4 shows the results of thisstudy in the T₁ ^(p) vs. S[1H].sup..5 form as discussed for the ¹²⁹ Xepresented in FIG. 3. The various errors associated with the ³ He studymake direct comparison with the ¹²⁹ Xe difficult. However, there aretrends linking the two studies worth noting.

The results for LDPE and PTFE agree extremely well with theory. However,the other materials in the ³ He study fall short of predicted T₁relaxation times. Of these materials, silicone, PP and HDPE areconsistent with short results observed in the ¹²⁹ Xe study.

This trend points to paramagnetic impurities in the material samples.These contaminants can include dust, fingerprints, Apiezon grease, andferrous impurities that may be trapped in the polymer material.Unfortunately, higher diffusion coefficients for lie result in muchlonger length scales (˜20 μm ³ He vs.˜1 μm ¹²⁹ Xe, Equation 2.23) forpolymer gas interaction. The greater mobility of gas atoms in thepolymer results in much deeper sampling of the polymer. This samplingcould significantly increase the probability of interaction withparamagnetic impurities if their distribution in the polymer isnon-uniform. For example, gas in silicone has a large diffusioncoefficient (DHe˜4e-5, DXe˜5e-6) relative to other polymers in thestudy. While the measured T₁ for silicone, PP, and HDPE was lower thanpredicted in both ¹²⁹ Xe and ³ He studies, the ³ He has a length scaleroughly 3 times that of ¹²⁹ Xe. This contaminant concern magnifies theimportance of sample preparation in the study of surface effects as wellas the preparation of containers used for hyperpolarized gases. Asdiscussed with the ¹²⁹ Xe study, sample preparation included only asurface cleaning, leaving any contaminants contained within the polymermatrix. One alternative can be to use acid baths to clean containers orcontainer materials to remove or minimize at least surface and proximatesub-surface impurities potentially embedded in the polymer matrix.

Of the remaining polymers in the ³ He study, only polyimide (PI) andnylon 6 show markedly different results between the two studies. Onedistinction that might explain this result is the difference betweenamorphous and semicrystalline polymers. LDPE, HDPE, and PP are amorphouspolymers that should exhibit uniform solubility. Alternatively,semicrystalline polymers such as PTFE, nylon 6, and PI might exhibitspatial diffusion and thus exhibit regional solubilities that differfrom the bulk solubility measured in the polymer lab.

A summary comparison of the predicted and measured results for ³ He ispresented in Table 4.3. (Detailed results in FIG. 5).

                  TABLE 4.3                                                       ______________________________________                                        Results of Polymer Relaxation Study for .sup.3 He                                       Pred.   Pred.                                                                 Υ (cm/                                                                        T.sub.1.sup.cc                                                                        Measured Υ                                                                      Measured T.sub.1.sup.cc                   S         min)    (min)   (cm/min)  (min)                                     ______________________________________                                        LDPE  0.0060  0.0012  170.98                                                                              0.0012 ± 0.00015                                                                     170.80 ± 21.22                       HDPE  0.0040  0.0008  252.40                                                                              0.0056 ± 0.00055                                                                     36.65 ± 3.66                         PP    0.0067  0.0013  154.81                                                                              0.0211 ± 0.00156                                                                      9.80 ± 0.77                         PTFE  0.1104  0.0158   13.09                                                                              0.0150 ± 0.00071                                                                     13.72 ± 0.65                         Nylon 6                                                                              .003    .0005  395   0.0026 ± 0.00034                                                                      79.98 ± 11.17                       Silicone                                                                            0.0340  0.0061   33.69                                                                              0.0386 ± 0.00169                                                                      5.36 ± 0.22                         PI    0.0300  0.0032   64.30                                                                              0.0055 ± 0.00054                                                                     37.58 ± 3.78                         ______________________________________                                    

O₂ Contamination

Impurities introduced into the test environment could also account formeasurement errors. Dust, fingerprints, and other contaminants may beintroduced into the test chamber when the chamber is opened to insertthe sample. All of these contaminants have a depolarizing effect that isnot included in the sorption model. The most significant confirmedcontaminant in the test environment is the presence of O₂ in the testchamber.

Because O₂ has a magnetic moment, it can relax hyperpolarized gases inthe same manner as protons. While O₂ affects ¹²⁹ Xe and ³ He similarly,the longer T₁ times associated with the ³ He study magnify any O₂contamination. For example, 1 Torr of O₂ in the chamber would generallynot be noticed on the time scale of the ¹²⁹ Xe study but would have aradical impact on ³ He studies. The effect of O₂ in the test chamber wasobserved on several occasions. It resulted in a non exponential decayrate many times faster than the predicted T₁ of the sample.

While in storage, oxygen from the atmosphere diffuses and sorbs into thepolymer sample. In order to remove this O₂ from the polymer, the sampleis preferably left under vacuum for a period of time before testing. Thetime period necessary for this degassing to take place can be calculatedif diffusion coefficients are available. Table 4.5 shows the degassingcalculations for 1 mm thick polymer samples with available O₂ diffusioncoefficients, assuming t≈(Z)² /D (Z=sample thickness).

                  TABLE 4.5                                                       ______________________________________                                        O.sub.2 Degassing Time for .sup.3 He Relaxation Studies                               D(O.sub.2)  Volume O.sub.2 in                                                                         Vacuum Time                                   Material                                                                              cm.sup.2 /s Polymer cc (STP)                                                                          Hr                                            ______________________________________                                        LDPE    6.80e-06    0.0201      0.41                                          HDPE    3.07e-06    0.0077      0.90                                          PP      1.95e-05    *           0.14                                          PTFE    8.11e-07    0.0893      3.43                                          Silicone                                                                              4.10e-05    0.1302      0.07                                          ______________________________________                                         *no S(O.sub.2) available for PP                                          

In determining the relaxation time (T₁) of a hyperpolarized noble gas ina polymer container equation 2.21, can be restated as: ##EQU28## where"V" is the container volume, "A" is the container surface area, "S" isthe Ostwald solubility of the noble gas in the polymer, "T₁ ^(p) " isthe relaxation time of the noble gas dissolved in the polymer matrix,and "D_(p) " is the diffusion coefficient of the noble gas in thepolymer. This quantitative analysis reveals that the relaxation time ofthe noble gas is inversely proportional to noble gas solubility in thepolymer. Indeed, and surprisingly, as noted above, the surface inducedrelaxation time is believed to be proportional to the square root of thenoble gas relaxation time in the polymer matrix.

Restating the multiple constants of equation 2.23 into a factor "C"results in: ##EQU29##

Thus, the relaxation rate of a noble gas in the polymer can be expressedas stated in equation (2.23b (I=proton spin)). ##EQU30##

Inserting this relaxation rate expression into equation (2.21') showsthat the dependence on diffusion coefficient disappears and results in asurface relaxation time "T₁ " which can be expressed by equation(2.23c). ##EQU31##

This expression can be used to predict the relaxation time ofhyperpolarized noble gases such as either ³ He or ¹²⁹ Xe on any polymersurface. As was pointed out in U.S. Pat. No. 5,612,103, perdeuterationof the polymer should lead to improvement in the noble gas relationtime. However, this improvement appears to be less than what waspreviously predicted. The gyromagnetic ratio γ_(D) of deuterium is 6.5times smaller than for hydrogen, and the spin "I" is 1. A comparison ofthe relaxation time of the noble gas in the perdeuterated polymer matrixversus its normal counterpart shows the following: ##EQU32##

However, this improvement in T_(p) translates into an overallimprovement in relaxation time of about 4 (the square root of 15.9).Thus, deuteration is still desired but perhaps is not as impressive aswas previously expected.

A comparison of ³ He relaxation with ¹²⁹ Xe relaxation on a givenpolymer surface can now be made using equation (2.23c) assuming that "b"does not vary substantially for the two gases as expressed in equation(2.31). ##EQU33##

For example, in low-density polyethylene ("LDPE"), the ratio of xenonsolubility to helium solubility is 107 and the ratio of γ_(Xe) /γ_(He)=0.37. Thus, the relaxation time of ³ He on a LDPE surface will benearly 40 times longer than for ¹²⁹ Xe.

Further, as noted above, the noble gas polarization level is notspatially uniform in the polymer. The polarization is constant for thegaseous phase but falls off exponentially with distance into thepolymer.

Therefore, it is important to note that especially in the case ofpolymer coatings, the thickness of the coating preferably exceeds thepolarization decay length scale "L_(p) " (equation 2.22) in order forthe gas depolarization time to depend on the polymer properties in apredictable way. For a coating thickness less than "L_(p) ", polarizedgas can sample the substrate underneath the polymer, and potentiallyundergo undesirably fast relaxation. Because "T_(p) " also dependslinearly on "D_(p)," the depolarization length scale is proportional tothe gas diffusion coefficient. Thus, especially for ³ He, which tends tohave a high diffusion constant, the polymer contact layer, or thethickness of the coating or film is preferably several times thecritical length scale. Preferably, the thickness is above about 16micrometers and more preferably at least 100-200 micrometers thick inorder to be effective. In fact, coatings that are substantially thinnerthan "L_(p) " can be more deleterious than having no coating at all,because the mobility of the noble gas once into the coating is reduced.As such, a noble gas dissolved in a thin coating can interact with thesurface underneath for a much longer period of time than if the coatingwere not present. Indeed, the probability of depolarization appears toincrease as the square of the interaction time.

The relatively long relaxation times achievable with polymers (coatingsor container materials) make the development of polymer bags forhyperpolarized gas storage appealing. Further, bags are an ideal storageand delivery device for magnetic resonance imaging using inhaledhyperpolarized ³ He because the gas can be completely extracted bycollapsing the bag. In contrast, a rigid container typically requires amore sophisticated gas extraction mechanism.

O₂ Induced Relaxation

When bags with long surface relaxation times are used, other relaxationmechanisms can become important. One of the most important additionalrelaxation mechanisms is due to collisions of the noble gas withparamagnetic oxygen as noted above. Saam et al. have shown that therelaxation time of ³ He due to collisions with paramagnetic oxygen canbe expressed as stated in equation (2.32).

    T.sub.1 [O.sub.2 ]=2.27 s amgt                             (2.32)

(Note amagat is abbreviated as "amgt") (1 amagat=2.689×10¹⁹ atoms/cm³,the density of an ideal gas at 273 K and 1 atm.). See B. Saam, W. Happerand H. Middleton, Nuclear relaxation of ³ He in the presence of O₂,Phys. Rev. A, 52, 862 (1995). Thus, a pressure of oxygen as small as1/1000 of an atmosphere can result in a ³ He relaxation time of only 38minutes even with perfect surfaces. Given this problem, tremendous careshould be taken to reduce the oxygen content in the storage containerthrough careful preconditioning of the container, such as by pumping andpure gas purging methods. However, even with preconditioning, a bag issusceptible to permeation of oxygen through the polymer which candisadvantageously build substantial oxygen concentration over time. Thevolume of oxygen transmitted through the polymer material depends onseveral factors, including the polymer-specific oxygen permeabilitycoefficient "Q_(O2) ". For small quantities of oxygen transfer, the rateof oxygen concentration build-up in the bag is nearly constant, and canbe expressed by equation (2.33). ##EQU34## "[O₂ ]" is the oxygenconcentration in the bag, "A" is the polymer surface area, "ΔP_(O2) " isthe oxygen pressure difference across the bag surface, "V_(bag) " is thevolume of the bag, "Δx" is the polymer thickness, and "Q_(O2) " is theoxygen permeability coefficient. Using equation (2.33) and a bag havingthe following characteristics (area=648 cm², volume=1000 cm³, Δχ=0.01χcm, P=0.2×10⁵ Pa, Q_(O2) (LDPE)=2.2×10⁻¹³ cm² /S Pa) gives a d/dt(O₂)value of about 2.8×10⁻⁷ amgt/s. Thus, a one hour duration (3600 seconds)will give a 1×10⁻¹³ amgt, which corresponds to a T₁ of about 38 minutes.For Tedlar™, the O₂ permeability is smaller (0.139×10⁻¹³ -158 times lesspermeable than LDPE). Thus, in this material, one hour of permeationwill give an O₂ induced T₁ of about 99 hours, but after 10 hours the T₁drops to only 10 hours. Thus, as an alternative to an O₂ shield placedover the inner layer, the contact surface layer itself can be formed asa polymer having reduced permeability to O₂ and/or with increasedthickness Δx.

Accordingly, oxygen-induced relaxation can quickly dominate surfacerelaxation even when careful gas handling techniques are employed.Therefore, in order to make polymer bags a viable storage medium,another layer of material is preferably used to suppress oxygenpermeability. So long as the thickness of polymer in contact with thepolarized gas is greater than L_(p), the secondary material used foroxygen permeability suppression does not need to be non-depolarizing. Ametal film such as aluminum can be very effective in such anapplication.

Materials

A comparison of the experimentally measured relaxation times to thetheoretical values reveals remarkable agreement for the polymer systemsfor which ¹²⁹ Xe solubilities are known. Theoretical relaxation timesare also calculated for ³ He on a variety of polymer surfaces/systems.The results are summarized in FIGS. 5 and 6. The relaxation times havebeen scaled to a 1 cm³ spherical container.

Note that the results for ¹²⁹ Xe in the fluoropolymer PTFE (Teflon™) arealso shown in FIGS. 5 and 6. For this case, for a one cubic centimeter("cm³ ") spherical container, the calculated T₁ was 5.65 min and theobserved relaxation time was 8.3 min. The calculations are identical tothose discussed previously except for the substitutions in the equationsand a subtle change in "b" due the larger size of the fluorine atomcompared to the hydrogen atom. The composition of the atomic structureof the material is different (i.e., fluorine not hydrogen atom). Infact, with the possible exception of Tedlar™ (polyvinylfluoride), mostfluoropolymers are not particularly good for the preservation of either¹²⁹ Xe or ³ He hyperpolarization. For example, the predicted T₁ for ³ Heon PTFE is only 13.1 minutes in a 1 cm³ sphere. This is due to arelatively high solubility of helium in most fluropolymers due to thatlarger void space in the polymer resulting from the large fluorineatoms. Furthermore, most common gasket materials such as Viton™, Kel-F™,and Kalrez™, are fluropolymers and can potentially be substantiallydepolarizing to ³ He compared to pure hydrocarbon gaskets such as thosecontaining polyolefins. Examples of preferred seal materials includepolyolefins such as polyethylene, polypropylene, and copolymers andblends thereof.

Because the shape of the container area can impact the rate ofdepolarization, it is preferred that container configurations beselected to maximize the free-gas volume of the container (V) whileminimizing the surface area (A) which contacts the hyperpolarized gas(that is, to decrease the value of the ratio A/V). More preferably, thecontainer is sized and configured to provide a A/V ratio of about lessthan 1.0, and even more preferably less than about 0.75. In oneembodiment, the container is substantially spherical, such as a roundballoon-like container.

Preferred polymers for use in the inventions described herein includematerials which have a reduced solubility for the hyperpolarized gas.For the purposes of the inventions herein, the term "polymer" to bebroadly construed to include homopolymers, copolymers, terpolymers andthe like. Similarly, the terms "blends and mixtures thereof" includeboth immiscible and miscible blends and mixtures. Examples of suitablematerials include, but are not limited to, polyolefins (e.g.,polyethylenes, polypropylenes), polystyrenes, polymethacrylates,polyvinyls, polydienes, polyesters, polycarbonates, polyamides,polyimides, polynitriles, cellulose, and cellulose derivatives andblends and mixtures thereof. It is more preferred that the coating orsurface of the container comprise a high-density polyethylene,polypropylene of about 50% crystallinity, polyvinylchloride,polyvinylflouride, polyamide, polyimide, or cellulose and blends andmixtures thereof.

Of course, the polymers can be modified. For example, using halogen as asubstituent or putting the polymer in deuterated (or partiallydeuterated) form (replacement of hydrogen protons with deuterons) canreduce the relaxation rate. Methods of deuterating polymers are known inthe art. For example, the deuteration of hydrocarbon polymers isdescribed in U.S. Pat. Nos. 3,657,363, 3,966,781, and 4,914,160, thedisclosures of which are hereby incorporated by reference herein.Typically, these methods use catalytic substitution of deuterons forprotons. Preferred deuterated hydrocarbon polymers and copolymersinclude deuterated paraffins, polyolefins, and the like. Such polymersand copolymers and the like may also be cross-linked according to knownmethods.

It is further preferred that the polymer be substantially free ofparamagnetic contaminants or impurities such as color centers, freeelectrons, colorants, other degrading fillers and the like. Anyplasticizers or fillers used should be chosen to minimize any magneticimpurities contacting or positioned proximate to the hyperpolarizednoble gas.

Alternately, the first layer or contact surface can be formed from ahigh purity (and preferably non-magnetic) metal. The high purity metalcan provide advantageously low relaxivity/depolarization resistantsurfaces relative to hyperpolarized noble gases. Preferred embodimentswill be discussed further below. Of course, the high purity metal filmcan be combined with the materials discussed above or can be used withother materials to form one or more layers to provide a surface orabsorption region which is resistant to contact depolarizationinteractions.

As noted above, any of these materials can be provided as a surfacecoating on an underlying substrate or formed as a material layer todefine a friendly contact surface. If used as a coating, the coating canbe applied by any number of techniques as will be appreciated by thoseof skill in the art (e.g., by solution coating, chemical vapordeposition, fusion bonding, powder sintering and the like). Hydrocarbongrease can also be used as a coating. As noted above, the storage vesselor container can be rigid or resilient. Rigid containers can be formedof Pyrex# glass, aluminum, plastic, PVC or the like. Resilient vesselsare preferably formed as collapsible bags, preferably collapsiblepolymer or metal film bags.

Containers

Turning now to the drawings, FIGS. 7 and 8 illustrate a preferredembodiment of a container 10 for hyperpolarized gas according to theinstant invention. FIG. 7 shows the container 10 in the collapsed(empty) position and FIG. 8 shows the container 10 when inflated(filled). As shown, the container 10 includes a front wall 12 and a rearwall 13. The walls 12, 13 are joined by a perimeter seal 15. The frontwall 12 also includes a coupling member 20 and an entry port 22. Thecoupling member is preferably configured to releasably attach to thehyperpolarizer apparatus and an end delivery device. Preferably, thecoupling member 20 and perimeter seal 15 are configured to withstandabout 0.5-3 atm of pressure, and more preferably about 0.8-1.25 atm ofpressure. Preferably, as shown, the coupling member 20 is attached tothe front wall via a seal 25 to facilitate the airtight arrangement ofthe interface between the wall 12 and the coupling member 20.

FIG. 9 illustrates a sectional view of the container 10. The front andrear walls 12, 13 define a chamber 30 which expands to receive aquantity of hyperpolarized gas therein. The entry port 22 is in fluidcommunication with the chamber 30. In operation, the hyperpolarized gasis directed through the entry port 22 into the chamber 30 therebyforcing the container 10 to expand (FIG. 8) and capture thehyperpolarized gas.

In a preferred embodiment, as shown in FIGS. 9 and 12, the walls 12, 13are configured with two layers 41, 44. The first layer 41 includes theinner contact surface 12a of the chamber 30 that holds and thus contactsthe hyperpolarized gas. As such, the hyperpolarized noble gas issusceptible to contact induced depolarization depending on the type ofmaterial and the depth of the material used to form this layer. Thus,this surface is preferably formed by a coating or a material layer witha sufficient thickness for preventing the hyperpolarized gas fromsampling the underlying substrate. Also, the surface should have a lowrelaxivity relative to the hyperpolarized gas. As such, both thematerial and the thickness are chosen and configured to inhibit thesurface induced depolarization of the gas. As regards the thickness, itis preferred that the thickness be greater than the critical decay scalelength L_(p) and more preferably is greater than a plurality of thedecay length scale. For example, for ³ He and HDPE, the critical lengthscale is about 8 μm so a preferred material layer depth is >about16-20μm.

Further, as regards the "low relaxivity", it is preferred that for ³ Hethe material have a relaxivity value less than about 0.0013 cm/min andmore preferable less than 0.0008 cm/min. For ¹²⁹ Xe, it is preferredthat the material have a relaxivity value less than about 0.012 cm/minand more preferably less than about 0.0023 cm/min. Similarly "reducedsolubility" is meant to describe materials for which the hyperpolarizedgas has a reduced solubility. Preferably, as regards ¹²⁹ Xe thesolubility is less than about 0.75, and more preferably less than about0.4. For ³ He the solubility is preferably less than about 0.03, andmore preferably less than about 0.01.

The second layer 44 includes the external surface 12b that is exposed toair which includes components which can be potentially degrading to thehyperpolarized gas in the chamber. For example, as discussed above,paramagnetic oxygen can cause depolarization of the gas if it migratesinto the contact surface 12a or the chamber 30. As such, it is preferredthat the second layer 44 be configured to suppress oxygen migration. Forexample, the second layer 44 can be formed as an oxygen resistantsubstrate, a metal layer, or metallized deposit or coating formed overanother layer. Preferably, the second layer prevents de-magnetizingamounts of O₂ from entering into the chamber after 24 hours at 1 atm.More preferably, for a desired T₁ of about 24 hours and after 24 hoursof permeation, it is preferred that the O₂ concentration be less thanabout 2.6×10⁻⁵ amgt. Thus, at 1 atm, for a 1 liter bag, it is preferredthat the container be configured to keep the O₂ concentration in thechamber below 0.003% of the total gas concentration. Of course, thesecond layer can be alternatively chosen or configured to shield otherenvironmental contaminants such as moisture. For example, in thisembodiment, a first layer may have a very low permeability for O₂ butmay be sensitive to moisture. The second layer can be configured with aprotective polyethylene coating to compensate for this property andprovide an improved T₁ like container.

In yet another alternative embodiment, the inner surface 12a can beconfigured as a high purity (non-magnetic) metal film applied to anunderlying substrate, polymer, or other container material. High puritymetal surfaces can provide even better protection against depolarizationrelative to other surfaces. Because the hyperpolarized gas contacts themetal, the underlying material does not have to have a low solubilityfor the hyperpolarized gas. In a preferred embodiment, the container isresiliently configured as a collapsible bag with the inner surface 12aformed from a high purity metal film (preferably a thickness within therange of about 10 nm-10 microns). As such, in this embodiment, the firstlayer 41 is the metallized layer and can provide the oxygenresistance/shield as well as protection against contact depolarization.Preferred metals include those that are substantially paramagneticallypure (i.e., they do not introduce magnetic moments) and resistant tocontact depolarization of the hyperpolarized gases. Stated differently,the metal used should be chosen to minimize the adsorption time of thegas on the metal surface, i.e., such that the noble gas has a lowadsorption energy on the metal surface. Examples of suitable materialsinclude, but are not limited to, aluminum, gold, silver, indium,beryllium copper, copper, and mixtures and blends thereof. As usedherein, "high purity" includes materials which have less than 1 ppmferrous or paramagnetic impurities and more preferably less than 1 ppbferrous or paramagnetic impurities.

In an additional embodiment, the inner surface 12a can be formed as ahybrid surface (a blend or side by side disposition of high purity metalfilm and polymer) or as a high purity metal formed over a polymersubstrate. As such, a metal film can be layered over a polymer with goodrelaxivity properties to compensate for cracks or gaps which may developin the metal film layer.

In another preferred embodiment, as shown in FIG. 9, the inner surface12a is formed directly by the inner wall of a polymer bag and the outersurface is formed by a metallized coating positioned over and directlycontacting the polymer bag. However, as illustrated in FIGS. 10 and 11,intermediate layers 42, 43 positioned between the inner layer 41 andouter layer 44 can also be used.

In FIG. 10, the container 10 has four layers 41, 42, 43, 44. As shown,the inner layer 41 is not a coating but is defined by the expandablepolymer (or modified polymer) bag having a thickness sufficient toinhibit contact depolarization. In this embodiment the intermediatelayers can be formed from any number of alternative materials,preferably resilient materials so as to contract and expand with theinner layer 41. In one embodiment (not shown) a bag with five layers isused: the first layer is 35 μm of HDPE; the second layer 42 is 35 μm ofpolyamide; the third layer 43 is 1 μm of aluminum; the fourth layer 44is 35 μm of polyvinylidene chloride; and the fifth layer (not shown) is35 μm of polyester. Advantageously, the multiple layers can provideadditional strength and/or puncture and pressure resistance. Of course,alternative materials and numbers of layers can also be employedaccording to the present invention. In one embodiment (not shown), acoating can be placed on the inner surface 12a of the polymer bag todefine the proper depth of the contact layer either alone or incombination with the thickness of the polymer bag. Of course, the twolayers can be formed as one layer if the container material employed hasa low-relaxivity for the hyperpolarized gas and if the material issufficiently impermeable to environmental contaminants such as O₂.Examples of such materials include but are not limited to PET(polyethylene terphthalate), PVDC (polyvinylidene dichloride),cellophane and polyacrylonitrile.

As shown in FIGS. 13-15, the container 10 also includes a sealing meansoperably associated with the entry port 22 and used to capture thehyperpolarized gas within the chamber 30. In the configuration shown inFIG. 13, the coupling member 20 includes a conduit 70 extendingoutwardly therefrom. Generally described, the sealing means closes offthe passage 22a (FIG. 3) in communication with the entry port 22,thereby retaining the hyperpolarized gas in the container. Examples ofsuitable sealing means include, but are not limited to, a clamp 72 (FIG.13) a heat seal 74 (FIG. 14) and a membrane seal 76 (FIG. 15).Alternatively, a valve, a stop cock, and other fittings and/or seals(gaskets, hydrocarbon grease, O-rings) (not shown) can be used tocontrol the release of the hyperpolarized gas. Preferably, care is takento insure all fittings, seals, and the like which contact thehyperpolarized gas or which are located relatively near thereto aremanufactured from materials which are friendly to polarization or whichdo not substantially degrade the polarized state of the hyperpolarizedgas. For example, as noted above, except for Tedlar™(polyvinylfluoride), most commercially available seals includefluoropolymers which are not particularly good for the preservation ofeither ¹²⁹ Xe or ³ He hyperpolarized gases because of the solubility ofthe material with the hyperpolarized gas.

Inasmuch as most common gasket materials are fluoropolymers, they canpotentially have a substantially depolarizing effect on the gas. Thiscan be especially acute with respect to ³ He. This can be attributed toa relatively high solubility of helium in most fluoropolymers due to thelarger void space in the polymer attributable to the large fluorineatoms. Indeed, preliminary tests indicate that materials of commonO-rings (such as Viton™, Kel-F™, ethylene-propylene, Buna-N™, andsilicone) exhibit far worse relaxation properties than pure polymers.Most conventional O-rings are so depolarizing that they can dominate therelaxation of an entire hyperpolarized gas chamber. Indeed, commercialethylene propylene- O-rings exhibit 1/3-1/2 the relaxation time comparedto pure LDPE with ¹²⁹ Xe. O-ring magnetic impurities can be introducedby such things as colorants and fillers and the like. Therefore, it ispreferred that the containers of the present invention employ seals,O-rings, gaskets and the like with substantially pure (substantiallywithout magnetic impurities) hydrocarbon materials such as thosecontaining polyolefins. Examples of polyolefins include polyethylene,polypropylene, copolymers and blends thereof. Additional suitable sealsinclude hydrocarbon grease and hydrocarbon gaskets and O-rings made frompolyethylene and the like. Thus, if a valve is used to contain the gasin the chamber 30, it is preferably configured with a magnetically pure(at least the surface) O-ring and/or with hydrocarbon grease. Of course,if fillers and plasticizers are employed, then it is preferred that theybe selected to minimize the magnetic impurities such as substantiallypure carbon black.

In an alternative embodiment, the O-ring seal can be configured with theexposed surface coated with a high purity metal as discussed for thecontainer surface. Similarly, the O-ring or seal can be coated or formedwith an outer exposed layer of a polymer at least "L_(p) " thick. Forexample, a layer of pure polyethylene can be positioned over acommercial available O-ring. One preferred O-ring material for ¹²⁹ Xe isa Teflon™ coated rubber O-ring above or a low-relaxivity polymer asdiscussed above.

FIGS. 13 and 14 illustrate preferred embodiments of a seal arrangement.

Each seals the fluid passage 22a by pinching the conduit 70 shut in atleast one position therealong. FIG. 13 shows the use of an externalclamp 72 and FIG. 14 shows the use of a redundant heat seal 74. Inoperation, each is easily employed with little impact on thepolarization of the gas in the container 10. For example, for theembodiment shown in FIG. 14, after the container 10 is filled withhyperpolarized gas, an in-process clamp (not shown) is inserted over theconduit 70 such that it closes off the passage 22a. Heat is applied tothe conduit 70 as the conduit wall is collapsed to provide a heat seal74 to at least one side of the in-process clamp. The bag is then readyto transport. Once at the desired delivery location site, the heat seal74 can be cut away and a temporary clamp can be placed on the conduit70. As shown in FIG. 17, the conduit 70 can be directly engaged with abreathing apparatus or patient interface 90. As illustrated in FIG. 18,the hyperpolarized gas 100 can be forced out of the bag and into theinterface 90 such as by externally depressing/compressing the walls ofthe container 10. Alternatively, the patient 92 can simply inhalethereby directing the gas 100 into the inhalation pathway 105.

Turning now to FIG. 15, in another embodiment, a membrane seal 76 ispositioned directly over the external portion of the entry port 22. Themembrane seal 76 can be attached by heat, or an anchoring member such asa polymer washer threadably attached over the peripheral portion of thecoupling member 22, preferably leaving the central portion 76aexternally accessible. In this embodiment, as shown in FIG. 19, thecontainer 10 can be transported to the use site and inserted directlyinto a patient interface 90'. Preferably, the membrane seal 76 isinserted into the interface 90' such that it is positioned internal tothe air tight coupling provided by the joint 130 between the couplingmember 20 and the interface 90'. Advantageously, the interface 90' caninclude a puncture 79 recessed within the receiving area to open thecentral portion of the membrane seal 76 after the coupling member 20forms the external joint 130 such that the container is sealed to theinterface 90'. This allows the gas in the container to be easilyreleased and directed to the patient. The gas can be easily extracted orforced out of the container 10 by depressing the walls 12, 13 of thecontainer 10 or via inhalation. Advantageously, such a configurationremoves the requirement for relatively complex or sophisticated gasextraction mechanisms and also reduces the amount of physicalmanipulation and/or interfaces required to deliver the gas to thesubject.

As shown in FIG. 16, a shipping box 80 is preferably used to hold thebag 10 during transport. This can help protect the bag from physicalhazards. In addition, it is preferred that the box 80 include magnetmeans to provide a desired static magnetic (substantially homogeneous)field around the hyperpolarized gas. In addition, or alternatively, thebox 80 can be configured to form a shield from undesirable straymagnetic fields as will be discussed further below.

In summary, the present invention provides containers which improve onthe relaxation time of the hyperpolarized gas. Preferably, the containeris sized and configured and the contact surface formed from a suitablematerial such that the hyperpolarized gas in the container has arelaxation time greater than about 6 hours and more preferable greaterthan about 20 hours for ³ He. Similarly, the container is preferablysized and configured such and the contact surfaces formed from asuitable material that the ¹²⁹ Xe hyperpolarized gas in the containerhas a relaxation time greater than about 4 hours and more preferablygreater than about 8 hours.

Shielding

Unless special precautions are taken, relaxation due to stray magneticfields can dominate all other relaxation mechanisms. Both gradients inthe static field experienced by the gas and low-frequency oscillatingmagnetic fields can cause significant relaxation. Based on recentexperience, oscillating fields are the biggest potential concern.

At all relevant pressures and field strengths, the relaxation rate dueto static field inhomogeneities is given by (2.40). ##EQU35## where "B₀" is the static applied field, "∇_(T) " is the transverse gradient ofthat field, "D₀ " is the diffusion constant of the hyperpolarized gas atone atmosphere, and "P" is the gas pressure. For 1 atmosphere of He (D₀is≈2 cm² /s) in the earth's field (0.5 Gauss), a transverse gradient of5 mG per cm leads to Γ∇_(B) ≈10⁻⁴ S⁻¹ and a gradient induced relaxationtime "T₁ " of approximately 1.5 hours. During transport, it is desirableto avoid inhomogeneous fields due to nearby objects. Calculations canestimate the types of gradient strengths that can be expected fromobjects like car frames and axles. Another way to be less sensitive tosuch unpredictable gradient relaxation is to apply an external field "B"which is sufficiently homogeneous (thus, not raising ∇_(T) B). In theprevious example, if a homogeneous field of even 10 G were applied, thesame 5 mG gradient would instead result in T₁ ≈600 hr. Preferably, thehomogenity is about 5×10⁻⁴ over a 1×1×1 cm cube.

In addition to static field gradients, oscillating magnetic fields cancause significant depolarization. Such oscillating fields can begenerated by car engines, power substations, and other large, currentcarrying entities. Incoherent fields with a correlation time (t_(c)<<1/γB_(noise)) can be shown to lead to negligible relaxation, thoughthey will likely contain spectral components which are resonant with thepolarized gas. However, there is evidence that automobile engines cangenerate coherent fields of up to about a milliGauss in the 500 Hz range(the resonant frequency of ¹²⁹ Xe in the earth's field). The resonantfrequency of ³ He in the earth's field is 1.6 Khz.

The relaxation rate due to coherent alternating current fields is givenby

    Γ.sub.AC =2γB.sub.AC                           (2.41)

For example, a 5 microGauss resonant field (B_(AC))leads to a ¹²⁹ Xerelaxation time of about 100 seconds. In order to minimize this rate,the AC field is preferably blocked, the static magnetic field (B₀) isincreased (to increase the resonant frequency of gas), or both.Preferably, AC fields are shielded by positioning a shield or shippingcontainer formed of ordinary metals proximate to (around) thehyperpolarized gas in the container. The skin depth or spatial decayconstant of an electromagnetic wave in a metal is given by

    δ=(ρ/πƒμ).sup.1/2                 (2.42)

where "ρ" is the resistivity of the shielding metal, "f" is thefrequency (in Hz) of the field, and "μ" is the permeability of themetal. Each skin depth "δ" reduces the external magnetic fieldassociated with the AC source B_(AC) by a factor of 1/e. To reduce"B_(AC) " by a factor of 100, preferably about five skin depths areused. At room temperature, the skin depth of aluminum is δ_(Al) (500Hz)=4 mm. Thus, for a factor of 100 reduction in AC field strength"B_(AC) " one can use approximately 3/4 inch of aluminum. Alternatively,the shield can use about 0.1 mm of ultra low carbon steel (by virtue ofits greater permeability). However, use of high permeability materialsmay also shield a large portion of the earth's magnetic field from thehyperpolarized sample, lowering its resonant frequency and increasingthe likelihood of depolarization. Again, application of a homogeneousstatic field proximate to the hyperpolarized gas can help by pushing theresonant frequency of the gas outside the bandwidth of common AC fields.For ¹²⁹ Xe, the static field is preferably at least about 20 gauss; andfor ³ He, the static field is preferably at least about 8 gauss. Thiswill shift the ¹²⁹ Xe resonant frequency to 23.6 Khz and the ³ Heresonant frequency to 25.6 Khz. Preferably the frequency will be above10 Khz.

When the hyperpolarized gas is ³ He, it is preferred that the sealedcontainer have a pressure in the range of about 1-10 atm (10 atm, 75hours). Higher pressures allow more product to be shipped in thecontainer and reduces the sensitivity of the hyperpolarized gas togradient relaxation, but the gas-gas collision relaxation can becomesubstantial. In contrast, for ¹²⁹ Xe, it is preferred that the gaspressure be about 1 atm or less, because higher pressures candramatically reduce the expected relaxation time of the hyperpolarized¹²⁹ Xe (10 atm, 5.6 hours). It is also preferred that the container beconfigured as a single dose unit, such as with 1 liter of ahyperpolarized gas product.

Preconditioning the Container

Preferably, due to susceptibility of the hyperpolarized to paramagneticoxygen as noted above, the storage container 10 is preconditioned toremove contaminants. That is, it is processed to reduce or remove theparamagnetic gases such as oxygen from within the chamber and containerwalls. For containers made with rigid substrates, such as Pyrex™ UHVvacuum pumps can be connected to the container to extract the oxygen.However, for resilient containers such as polymer bag containers, aroughing pump can be used which is typically cheaper and easier than theUHV vacuum pump based process. Preferably, the bag is processed withseveral purge/pump cycles, eg., pumping at or below 40 mtorr for oneminute, and then directing clean buffer gas (such as nitrogen) into thecontainer at a pressure of about one atm or until the bag issubstantially inflated. The oxygen partial pressure is then reduced inthe container. This can be done with a vacuum but it is preferred thatit be done with nitrogen. Once the oxygen realizes the partial pressureimbalance across the container walls it will outgas to re-establishequilibrium. Typical oxygen solubilities are on the order of 0.01-0.05;thus, 95-99% of the oxygen trapped in the walls will transition to a gasphase. Prior to use, or filling, the container is evacuated, thusharmlessly removing the gaseous oxygen. Unlike conventional rigidcontainers, polymer bag containers can continue to outgas (trapped gasescan migrate to the chamber because of pressure differentials between theouter surface and the inner surface) even after the initial purge pumpcycles. Thus, care should be taken to minimize this behavior especiallywhen the final filling is not temporally performed with thepreconditioning of the container. Preferably, a quantity of clean fillergas is directed into the bag (to substantially equalize the pressurebetween the chamber and ambient conditions) and sealed for storage inorder to minimize the amount of further outgassing that may occur whenthe bag is stored and exposed to ambient conditions. This shouldsubstantially stabilize or minimize any further outgassing of thepolymer or container wall materials. In any event, the filler gas ispreferably removed (vacuumed) prior to final filling with thehyperpolarized gas. Advantageously, the container of the instantinvention can be economically reprocessed (purged, cleaned, etc.) andreused to ship additional quantities of hyperpolarized gases.

It is also preferred that the container or bag be sterilized prior tointroducing the hyperpolarized product therein. As used herein the term"sterilized" includes cleaning containers and contact surfaces such thatthe container is sufficiently clean to inhibit contamination of theproduct such that it is suitable for medical and medicinal purposes. Inthis way, the sterilized container allows for a substantially sterileand non-toxic hyperpolarized product to be delivered for in vivointroduction into the patient. Suitable sterilization and cleaningmethods are well known to those of skill in the art.

Measuring Gas Solubility in a Polymer or Liquid

In the past, measuring gas solubilities of most polymers has been timeconsuming and difficult, and in the case of helium, usually inaccurate.However, as discussed above, the hyperpolarized gas relaxation time, T₁,is now determined to be proportional to gas solubility. Advantageously,due to the recognition and determination of the relationships discussedabove, hyperpolarized noble gases such as ³ He and ¹²⁹ Xe can be used todetermine or measure the gas solubility in a polymer or liquid. Thisinformation can be valuable for quickly assessing the structures of thepolymer. In addition, a given polymer sample can be evaluated using both¹²⁹ Xe and ³ He gases, as each can give complimentary information. Forexample, ³ He will sample a greater depth of the polymer based on itsgreater diffusion coefficients.

Preferably, as shown in FIG. 20, a first quantity of a hyperpolarizedgas is introduced into a container (Block 300). A first relaxation timeis measured of the 25 hyperpolarized gas in the container (Block 310). Aselected material sample is positioned in the container (Block 320). Asecond quantity of a hyperpolarized noble gas is introduced into thecontainer (Block 330). A second relaxation time is measured associatedwith the sample and the gas in the container (Block 340). The gassolubility is determined based on the difference between the tworelaxation times (Block 350). Preferably this is determined according toequation (2.23c). The material sample can be a physical or solid sampleor a liquid as described above.

Although the sample used above was a geometrically fixed polymer sample,the method can also be used to determine gas solubilities in liquids orfluids. For example, instead of placing a polymer sample into thechamber, a liquid can be introduced. The liquid will preferably beintroduced in a quantity which is less than the free volume of thechamber as it will conform to the shape of the chamber to define anassociated volume and surface area. The polarized gas can then bedirected into the chamber with the liquid and the relaxation ratedetermined due to the specific liquid. This can be especially helpful informulating carrier substances for injection formulations ofhyperpolarized ¹²⁹ Xe and ³ He.

EXAMPLES

In the examples provided below, the polymer contact surface is assumedto be present at a depth corresponding to a plurality of critical lengthscales as discussed above.

Example 1 ³ He LDPE/HDPE Bag

An exemplary one liter patient delivery bag, such as is shown in FIG. 7,is a 7 inch×7 inch square. The expected T₁ for ³ He can be determinedusing (Equation 2.4) and the theoretical relaxivity of LDPE for ³ Hequoted in Table 4.3. The associated area (A=2*18 cm*18 cm) is 648 cm²,the volume is 1000 cubic centimeters, and the relaxivity is 0.0012cm/min. Equation 2.4 leads to a T₁ of about 1286 min or 21.4 hours foran LDPE bag configured and sized as noted above (absent other relaxationmechanisms). For a bag made of HDPE, which has a lower relaxivity valueof about 0.0008 cm/min (attributed to the lower ³ He solubility), the T₁is estimated at 32 hours. In deuterated HDPE the T₁ is expected to beabout 132 hours.

Example 2 ¹²⁹ Xe LDPE/Nylon Bag

The same 1 liter LDPE patient delivery bag as described in Example 1contains hyperpolarized ¹²⁹ Xe. Volume and surface area are the same butthe theoretical relaxivity is 0.0419 cm/min (Table 4.2) for ¹²⁹ Xe onLDPE. The relaxivity is much higher because of the higher solubility of¹²⁹ Xe in LDPE compared to He (S_(Xe) =0.68 vs S_(He) =0.006). For thisconfiguration, T₁ is estimated at 36.8 minutes. Similarly, for themeasured relaxivity for Nylon-6 of 0.0104 cm/min, predict T₁ ispredicted to be about 148 min or about 2.4 hours. This value is close towhat has been measured for the presently used Tedlar™ bags.

Example 3 Metal Film Surface

In this example, metal film coatings are used as the contact surface.The 7"×7" square bag described in Example 1 is employed but coated orformed with high purity aluminum on its internal contact surface (thesurface in contact with the hyperpolarized gas). The relaxivity of highpurity aluminum for ¹²⁹ Xe has been recently measured to be about0.00225 cm/min. (One readily available material suitable for use isReynold's™ heavy duty freezer foil). Doing the calculation, one canobtain a container with an extended T₁ for xenon of about 11.43 hours.This is a great improvement in T₁ for Xe. Similarly, the use of suchmetal film surfaces for 3He can generate T₁ 's in the range of 1000's ofhours (the container no longer being a limiting factor as these T₁ 'sare above the theoretical collisional relaxation time described above).Metals other than aluminum which can be used include indium, gold, zinc,tin, copper, bismuth, silver, niobium, and oxides thereof. Preferably,"high purity" metals are employed (i.e., metals which are substantiallyfree of paramagnetic or ferrous impurities) because even minute amountsof undesirable materials or contaminants can degrade the surface. Forexample, another high purity aluminum sample tested had a relaxivity ofabout 0.049 cm/min, a full 22 times worse than the sample quoted above.This is most likely due to the presence of ferrous or paramagneticimpurities such as iron, nickel, cobalt, chromium and the like.Preferably, the metal is chosen such that it is well below 1 ppm inferrous or paramagnetic impurity content.

Example 4 Multiple Materials

Using the bag configured as noted in Example 1, one can determine theeffects of the addition of multiple materials. For example, a 5 cm²silicone gasket positioned on the 1 liter deuterated HDPE bag (describedin Example 1 (for ³ He)) with a starting T₁ of 132 hours will reduce thecontainer's associated relaxation time. As pointed out in Equations 2.5,2.6, relaxation rates are additive. Thus, to properly determine thecontainer or equipment relaxation time, the relaxivities andcorresponding surface areas of all the materials adjacent the freevolume should be evaluated. The hypothetical silicone gasket, with anexemplary area "A" of 5 cm², the measured relaxivity of 0.0386 cm/min(p. 47, table 4.3), and free volume still at 1000 cc, gives a relaxationrate of about 1.9×10⁻⁴ /min. Adding the rate due to the bag itself(1.3×10⁻⁴ /min) yields a total rate of about 3.2×10⁻⁴ /min which isinverted to get a T₁ of about 52 hours. Therefore, it is apparent thatadding a very small surface area of a poor material can drasticallyshorten the T₁ despite the fact that most of the container material isgood. Of course, real life O-ring materials can have relaxivities anorder of magnitude higher than the one described, making the situationeven worse. Thus, it is important to use substantially pure (impurityfree) materials. The relaxivity for an available "off the shelf"silicone O-ring for ¹²⁹ Xe was measured at about 0.2-0.3 cm/min. Forexample, using the measured ¹²⁹ Xe relaxivity numbers for the ³ Hedeuterated HDPE container will reduce the 132 hour bag down to just 15hours (a full order of magnitude deterioration). The key is that everygasket, coupling, valve, tubing or other component that is added to thebag or container (especially those that are in fluid communication withthe hyperpolarized gas) is preferably made of the friendliest possiblematerial relative to the hyperpolarized state.

Example 5 Measurement of Specific Material Properties

Measurement of specific material properties such as the relaxivities ofmaterials is described above. For example, as noted in equation 2.5,relaxation rates attributed to various relaxation mechanisms areadditive. Therefore, in order to measure the specific material property,a spin-down chamber such as that described herein can be used todetermine two relaxation times for a hyperpolarized gas. Using thechamber consisting of two hemispheres sealed with an O-ring, the chamberis closed, HP ("hyperpolarized gas") is introduced therein, and therelaxation time T₁ is measured. Then the chamber is opened, a sample ofknown surface area is inserted, and the process is repeated to measure anew T₁. The new T₁ will be less than the old because a new relaxingsurface has been added while keeping the free volume roughly the same.The difference between the two relaxation times is attributed to therelaxivity of the added material specimen. Thus, the difference can beused to calculate the material relaxivity using equation (2.10).

Example 6 Validation of the Sorption Model

FIGS. 4.1 and 4.2 show the calculated and experimental T₁ values for ¹²⁹Xe and ³ He, respectively, in a 1 cc sphere for different surfacematerials as plotted against the product of solubility (S) and thesquare root of the molar density of protons in the material matrix[1H].sup..5. The 1 cc sphere value incorporates both volume and surfacearea and is a useful T₁ metric corresponding to conventionalevaluations, and as such is typically more readily descriptive than therelaxivity parameters described herein. The T₁ value according toequation (2.23c) depends on a number of fixed constants and then dependsinversely on gas solubility and the square root of the protonconcentration. Experimental values of the measured one cubic centimetersphere T₁ (T₁ ^(cc)) for all the polymers are plotted as well and showsubstantial agreement between theory and experiment, thus validating thesorption model described herein.

The foregoing is illustrative of the present invention and is not to beconstrued as limiting thereof. Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. In the claims, means-plus-function clause are intended tocover the structures described herein as performing the recited functionand not only structural equivalents but also equivalent structures.Therefore, it is to be understood that the foregoing is illustrative ofthe present invention and is not to be construed as limited to thespecific embodiments disclosed, and that modifications to the disclosedembodiments, as well as other embodiments, are intended to be includedwithin the scope of the appended claims. The invention is defined by thefollowing claims, with equivalents of the claims to be included therein.

What is claimed is:
 1. A resilient container for holding hyperpolarizedgas, comprising:a compressible body comprising at least one collapsiblewall and an internal gas holding chamber, wherein said wall changes itsshape responsive to the introduction of gas into and out of saidinternal chamber such that said wall has a collapsed configurationassociated with the absence of a gas held in said internal chamber andan expanded configuration associated with the presence of a sufficientquantity of gas held in said internal chamber, wherein said at least onewall comprises: a first layer of a first material configured to definethe inner surface of said internal chamber; a second layer of a secondmaterial attached to and positioned to overlie said first layer suchthat said first layer is between said second layer and said internalchamber; a sealable port positioned in said wall in fluid communicationwith said internal chamber for directing gas in and out of said internalgas holding chamber; and a quantity of hyperpolarized gas positioned insaid internal gas holding chamber.
 2. A resilient container according toclaim 1, wherein at least one of said first and second layer materialsis an oxygen shielding material, and wherein said first and secondlayers are concurrently responsive to the application of pressure.
 3. Aresilient container according to claim 2, wherein said first layer has athickness sufficient to inhibit the hyperpolarized gas from exiting saidfirst layer into said second layer, and wherein said first layermaterial has a low relaxivity for said hyperpolarized gas.
 4. Aresilient container according to claim 3, wherein said first layercomprises a polymer gas-contacting surface.
 5. A resilient containeraccording to claim 2, wherein said hyperpolarized gas is ³ He, andwherein said first layer material is chosen from the group consisting ofpolyolefin, polystyrene, polymethacrylate, polyvinyl, polydiene,polyester, polycarbonate, polyamide, polyimide, polynitriles, celluloseand cellulose derivatives, and blends and mixtures thereof.
 6. Aresilient container according to claim 5, wherein said first material isperdeuterated or partially perdeuterated.
 7. A resilient containeraccording to claim 6, wherein said first layer material is substantiallyfree of paramagnetic contaminants.
 8. A resilient container according toclaim 2, wherein said first layer material comprises a copolymer.
 9. Aresilient container according to claim 1, wherein said first layermaterial is chosen from the group consisting of high-densitypolyethylene, polypropylene having about 50% crystallinity,polyvinylfluoride, polyamide, polyimide, polynitriles, and cellulose,and blends and mixtures thereof.
 10. A resilient container according toclaim 9, wherein said first layer material is at least partiallyperdeuterated.
 11. A resilient container according to claim 1, whereinsaid first layer material comprises a high purity metal.
 12. A resilientcontainer according to claim 1, wherein said first layer materialcomprises a material chosen from the group consisting of aluminum,indium, gold, zinc, tin, copper, bismuth, silver, niobium, and oxidesthereof.
 13. A resilient container according to claim 1, wherein saidhyperpolarized gas is ³ Helium, and wherein said first material has arelaxivity value of less than about 0.0013 cm/min.
 14. A resilientcontainer according to claim 1, wherein said hyperpolarized gas is ¹²⁹Xe, and wherein said first material has a relaxivity value of less thanabout 0.012 cm/min.
 15. A resilient container according to claim 1,wherein said hyperpolarized gas is ³ He, and wherein said gas in saidcontainer has a relaxation time longer than about 6 hours.
 16. Aresilient container according to claim 1, wherein said hyperpolarizedgas is ³ He, and wherein said hyperpolarized gas in said container has arelaxation time longer than about 20 hours.
 17. A resilient containeraccording to claim 1, wherein said hyperpolarized gas is ¹²⁹ Xe, andwherein said hyperpolarized gas in said container has a relaxation timelonger than about 4 hours.
 18. A method for determining thehyperpolarized gas solubility in a material such as a polymer or fluid,comprising the steps of:introducing a first quantity of hyperpolarizedgas into a container; measuring a first relaxation time of thehyperpolarized gas in the container; positioning a sample of a desiredmaterial in the container; introducing a second quantity of thehyperpolarized noble gas into the container; measuring a secondrelaxation time of the hyperpolarized gas in the container; anddetermining the gas solubility of the sample based on the differencebetween the first and second relaxation times.
 19. A resilient containerfor holding a quantity of hyperpolarized gas therein, said containercomprising:a resilient body defined by at least one wall comprisinginner and outer surfaces configured to define a gas holding chamber suchthat said body wall has a first collapsed position and a second inflatedposition associated with an unfilled and filled chamber, respectively;and a quantity of hyperpolarized noble gas held in said chamber; whereinsaid resilient body wall inner surface comprises a metallic materialwhich defines the gas-contacting surface and which inhibitscontact-induced polarization loss of said hyperpolarized gas held insaid chamber; and wherein said resilient body is configured to inhibitthe migration of oxygen into said chamber.
 20. A resilient containeraccording to claim 19, wherein said wall inner surface is formed of ahigh purity metal.
 21. A resilient container according to claim 19,wherein said wall outer surface is formed of a high purity metal.
 22. Aresilient container according to claim 19, wherein said wall includes afirst layer of a first material and a second layer of a second material,said second material being different from said first material, saidsecond layer positioned on said inflatable body such that said firstlayer is positioned between said second layer and said chamber, andwherein said first and second layers are concurrently responsive to theapplication of pressure onto said resilient body.
 23. A resilientcontainer according to claim 22, wherein said first layer comprises amaterial chosen from the group consisting of: polyolefin, polystyrene,polymethacrylate, polyvinyl, polydiene, polyester, polycarbonate,polyamide, polyimide, polynitriles, cellulose and cellulose derivatives,and blends and mixtures thereof, and wherein said metallic inner surfaceis formed onto said first layer material.
 24. A resilient containeraccording to claim 23, wherein said first layer material is at leastpartially perdeuterated.
 25. A resilient container according to claim23, wherein said first material is substantially free of paramagneticcontaminants.
 26. A resilient container according to claim 22, whereinsaid container chamber has an internal volume (V) and an internalsurface area (A), and wherein said container is sized such that theratio of A to V is less than about 0.75 cm⁻¹.
 27. A resilient containeraccording to claim 22, wherein said wall includes at least oneadditional intermediate layer sandwiched between said first and secondlayers.
 28. A resilient container according to claim 22, wherein saidfirst layer is a metal film layer.
 29. A resilient container accordingto claim 22, wherein said first layer material comprises a copolymer,and wherein said metallic inner surface is deposited onto said firstlayer material.
 30. A resilient container according to claim 22, whereinsaid first layer material is chosen from the group consisting of:high-density polyethylene, polypropylene having about 50% crystallinity,polyvinylfluoride, polyamide, polyimide, polynitriles, and cellulose,and blends and mixtures thereof, and wherein said metallic inner surfaceis formed onto said first layer material.
 31. A resilient containeraccording to claim 30, wherein said first material is perdeuterated orpartially perdeuterated.
 32. A resilient container according to claim22, wherein said first layer material is a high purity metal whichdefines said metallic inner surface.
 33. A resilient container accordingto claim 32, wherein said first layer comprises a material chosen fromthe group consisting of: aluminum, indium, gold, zinc, tin, copper,bismuth, silver, niobium, and oxides thereof.
 34. A resilient containeraccording to claim 19, wherein said hypcrpolarized gas is ³ Helium, andwherein said inner surface material has a relaxivity value of less thanabout 0.0013 cm/min.
 35. A resilient container according to claim 19,wherein said hyperpolarized gas is ¹²⁹ Xe, and wherein said innersurface material has a relaxivity value of less than about 0.012 cm/min.36. A method according to claim 18, wherein said sample is astructurally fixed sample having a known geometric shape with a surfaceformed of the desired material.
 37. A method according to claim 18,wherein said sample is a quantity of fluid filling a portion of the freevolume in the chamber.
 38. A method for filling a container having acollapsible body, comprising the steps of:providing a container bodywith a gas holding chamber such that the container body expands andcollapses in response to the filling and purging of gas directed intoand out of the chamber, respectively, wherein the internalgas-contacting surface of the container body is formed with a highpurity metal to inhibit the contact depolarization attributed thereto;directing a quantity of hyperpolarized gas into said container body;expanding the container body by accumulating a quantity ofhyperpolarized gas in the gas holding chamber to hold the hyperpolarizedgas therein; and sealing the container body to retain the accumulatedquantity of gas therein.
 39. A method according to claim 38, whereinsaid forming step comprises positioning a port and a seal for closingsaid port in said container body such that said gas holding chamber isin fluid communication therewith, said method further comprising thestep of configuring the container body such that it inhibits themigration of oxygen into said gas holding chamber when said port isclosed.
 40. A method according to claim 38, wherein said hyperpolarizedgas is ³ Helium, and wherein said internal gas-contacting surfacematerial has a relaxivity value of less than about 0.0013 cm/min.
 41. Amethod according to claim 38, wherein said hyperpolarized gas is ¹²⁹ Xe,and wherein said internal gas-contacting surface material has arelaxivity value of less than about 0.012 cm/min.
 42. A method accordingto claim 38, wherein said container body comprises a plurality ofoverlying material layers attached theretogether so as to beconcurrently responsive to the application of pressure thereagainst. 43.A method according to claim 42, wherein each of said plurality ofmaterial layers is formed of different materials.
 44. A method accordingto claim 42, wherein said hyperpolarized noble gas held in saidcontainer is ³ He, and wherein said hyperpolarized ³ He gas in saidcontainer has a relaxation time longer than about 6 hours.
 45. A methodaccording to claim 42, wherein said hyperpolarized noble gas held insaid container is ³ He, and wherein said hyperpolarized ³ He gas in saidcontainer has a relaxation time longer than about 20 hours.
 46. A methodaccording to claim 42, further comprising the step of substantiallypurging the bag of oxygen before said directing step.